Catalogo harvard apparatus 5

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the most comprehensive line for

Behavioral Research Locomotor Activity & Exploration Sensory Motor & Coordination Analgesia Learning & Memory Anxiety & Depression Reward & Addiction Food & Drink/Metabolism Call to receive other Cell Biology & Electrophysiology

Animal, Organ & Cell Physiology

Behavioral Research

catalogs of interest Micro/Nano Fluidics

Electroporation & Electrofusion

Molecular Sample Preparation


behavioral research catalog

Panlab, now a subsidiary of Harvard Apparatus,

Modular Operant Box, superior versatility, see page 75

manufactures and distributes high quality equipment for the biological sciences. For over 30 years, our team covers all stages of development – from design to manufacturing, software to hardware, technical and scientific support. Panlab/Harvard Apparatus is your reliable source for the most comprehensive solutions to your application needs - our offerings include the following application areas: video tracking, activity/

acquisition

exploration, sensory motor, analgesia, memory, anxiety, metabolism, non-invasive blood pressure, and isolated physiology systems. Our team is ready to adapt, improve or develop new or pre-existing lines to meet our customer’s changing requirements.

Startle/Fear Combined System, advanced technology for better results, see page 71

SMART with M ultip excepti onal vid le Arena Exten sion, eo track ing dete softwar c ti e, see p on age 6

Species Guide for Behavioral Systems

rabbit

guinea pig

rat

mouse

insect

fish

To help you become more familiar with our product line, Panlab/Harvard Apparatus has added small animal icons for every product. These icons will help guide you to which species can be used with each system. Above is a sample of the animal icons you will see throughout this catalog.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Table of Contents Products

Page No.

Selection Guide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5 Video Tracking SMART Video-Tracking System . . . . . . . . . . . . . . . . .6 – 7 Smart JUNIOR Video-Tracking System . . . . . . . . . . .8 – 9 Activity & Exploration IR Actimeter for Activity & Exploration . . . . . . . . .15 – 16 ActiTrack Software IR Actimeter . . . . . . . . . . . . . . . . . . .17 Sensory Motor Rota Rods for Motor Coordination . . . . . . . . . . . . . . . . .22 Grip Strength Meters . . . . . . . . . . . . . . . . . . . . . . . .23 – 24 Rodent Activity Wheel . . . . . . . . . . . . . . . . . . . . . . .25 – 26 Treadmills . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27 – 28 Rotameter . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29 Rodent Shocker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30 Analgesia Locomotor Activity and Exploration Selection Guide10 – 14 Sensorimotor and Coordination Selection Guide .18 – 21 Spatial Place Preference Box

Analgesia Selection Guide . . . . . . . . . . . . . . . . . . . .31 – 34 Locomotor Activity and Exploration Selection Guide . . . Tail Flick Analgesia Meter . . . . . . . . . . . . . . . . . . . .35 – 36 Hot and Hot/Cold Plate Meters . . . . . . . . . . . . . . . .37 - 39 Thermal Place Preference/Gradient Tests . . . . . .40 – 41 Electronic Von Frey . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .42 Heat-Flux Infrared Radiometer . . . . . . . . . . . . . . . . . . . .43 Plantar Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .44 – 46 Rat Paw Pressure Analgesia Meter . . . . . . . . . . . . . . . .47 Plethysmometer for Evaluating Paw Volume . . . .48 – 49 Dynamic Weight Bearing Test . . . . . . . . . . . . . . . . . . . . .50 Pressure Application Measurement (PAM) . . . . . . . . . .52 Pressure Application Measurement (PAM) . . . . . . . . . .52

SMART VideoTracking System


Oxylet System for Respiratory Metabolism

Products (continued)

Page No.

Memory & Attention Learning and Memory Selection Guide . . . . . . . . .53 – 60 Attention Selection Guide . . . . . . . . . . . . . . . . . . . .61 – 62

ActiTrack Software IR ActimeterRelated Tracking Anxiety Locomation & Exploration

Shuttle Boxes for Active/Passive Avoidance . . . .63 – 64 ShutAvoid Software for Active & Passive Avoidance . . . . . . . . . . . . . . . . . .65 – 66 Circular Pool . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .67 – 68 Radial Maze & Mazesoft-8 Software . . . . . . . . . . .69 – 70 Startle and Fear System & Software . . . . . . . . . . .71 – 74 Modular Operant Box for Operant Conditioning . .75 – 76 PackWin Software . . . . . . . . . . . . . . . . . . . . . . . . . . .77 – 78 5/9 Holes for Attention Performance . . . . . . . . . . . . . . .79 Passive Avoidance Box . . . . . . . . . . . . . . . . . . . . . .80 – 81 Anxiety & Depression Anxiety Selection Guide . . . . . . . . . . . . . . . . . . . . . .82 – 85 Depression Selection Guide . . . . . . . . . . . . . . . . . .86 – 87 Elevated Plus Maze & MAZESOFT-4 Software . . .88 – 89 Open Field & Black and White Boxes . . . . . . . . . . . . . .90 Small Animal Treadmill

Aron Test for Screen Anxiolytic Substances . . . . . . . .91 Black and White Test for Evaluating Anxiety . . . . . . . .92 Vogel Test for Screening Anxiolytic Effects of Drugs .93 Tail Suspension Test for Screening Antidepressant Activity . . . . . . . . . . . . . . . . .94 Addiction & Reward

Metabolism

Reward & Addiction Selection Guide . . . . . . . . . . .95 - 97

Food and Drink/Metabolism Selection Guide . .102 – 104

Place Preference Boxes . . . . . . . . . . . . . . . . . . . . . . . . . .98

Oxylet System for Respiratory Metabolism . . . .105 – 107

Spatial Place Preference . . . . . . . . . . . . . . . . . . . . . . . . .99

Metabolism Software . . . . . . . . . . . . . . . . . . . . . . . . . . .108

PPCWIN Software . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .100

PheComp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .109 – 110

Self-Administration Box . . . . . . . . . . . . . . . . . . . . . . . . .101

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Do you have a technical question?

Our staff of scientists have the answers you need!

In addition to our high quality research products, Panlab/Harvard Apparatus is proud to offer unparalleled technical sales for both pre- and post-sales. Our technical staff scientists are happy to help answer any questions you may have or assist with system configurations.

Contact us or visit our websites for access to:

Research articles Product Specifications Working Procedures

Demonstration Videos Instruction Manuals Application Sheets

www.harvardapparatus.com or www.panlab.com 4

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


selection guide Research Area

Experimental Test

Hardware

Software

Video Tracking

Video-Tracking Studies

Activity & Exploration

Locomotor Activity/Rearing Open Field Test Calorimetry, Food & Drink, Activity & Rearing Hole-Board Test Response to Novelty Voluntary Exercise Coordination and Equilibrium Test Rotation After Lesioning Grip Strength Exercise Training Startle Response Tail Flick Test Hot Plate Test Hot/Cold Plate Test Randall Selitto Test Inflammation Incapacitance Test Von Frey Test Passive Avoidance Test Active Avoidance Test Aron Test Morris Water Maze Radial Maze Test T-Maze Test Object Recognition Test Odor Recognition Test Fear Conditioning Test Fear Potentiated Startle Reflex Test Operant Procedures 5/9 Hole Test Prepulse Inhibition of Startle Reflex 5/9 Hole Test Operant Procedures Open Field Test Locomotor Activity/Rearing Elevated Plus Maze Test Black and White Box Test Vogel Test Geller-Seifter Test Forced Swimming Test Tail Suspension Test Place Preference Test

Frame Grabber Board Camera IR Actimeter Open Field Chamber Oxylet

SMART SMART and Smart JUNIOR SeDaCom or ActiTrack SMART or Smart JUNIOR Metabolism

IR Actimeter Open Field Chamber Rodent Activity Wheel Rota Rod Rotameter Grip Strength Meter Treadmill Startle and Freezing Combined System Tail Flick Meter Hot Plate Meter Hot/Cold Plate Test Meter Rat Paw Pressure Plethysmometer Incapacitance Test Meter Electronic VonFrey Passive Box Shuttle Box Aron Box Circular Pool Radial Maze T-Maze Open Field Chamber

SeDaCom or ActiTrack SMART or Smart JUNIOR Multicounter or SeDaCom SeDaCom SeDaCom SeDaCom SeDaCom Startle Software SeDaCom SeDaCom SeDaCom SeDaCom SeDaCom SeDaCom SeDaCom Programmer or ShutAvoid Programmer or ShutAvoid

Sensory Motor

Analgesia & Pain

Learning & Memory

Attention

Anxiety

Depression Addiction & Reward

Social Behavior Metabolism

Self-Administration Social Interaction Respiratory Metabolism Food & Drink Intake Compulsive Behavior

Startle and Freezing Combined System Startle and Freezing Combined System Modular Operant Box 5/9 Hole Box Startle and Freezing Combined System 5/9 Hole Box Modular Operant Box Open Field Chamber IR Actimeter Elevated Plus Maze Black and White Box Vogel Test Modular Operant Box Cylinder Tail Suspension Test System Place Preference Box Spatial Place Preference Self-Administration Box Open Field Chamber Oxylet FooDrink PheComp PheComp

SMART or Smart JUNIOR Mazesoft-8 or SMART SMART or Smart JUNIOR SMART SMART Freezing Software Startle Software PACKWIN PACKWIN Startle Software PACKWIN PACKWIN SMART or Smart JUNIOR ActiTrack SMART or Smart JUNIOR PPCWIN or SMART PACKWIN PACKWIN SMART PPCWIN PPCWIN or SMART PACKWIN SMART with Social Interaction Module Metabolism and Meta-Oxy Module Metabolism and Meta-Int Module Compulse Compulse


Video Tracking

SMART Video-Tracking System for Automated Recording of Animal Behavior

Key Features

➤ Flexible and precise analysis of animal behavior ➤ Optimized tracking in low contrast conditions

➤ Automated detection of head, center mass and base-tail with Triwise technology option ➤ Highly user-friendly

➤ Digital video file analysis capabilities ➤ Entirely configurable data report

➤ Zone-dependent camera settings ➤ Day/night cycle control system

➤ Immobility detection for forced-swimming test and freezing ➤ User defined criteria for zone entry with Triwise technology option

Parameters Measured

➤ Animal trajectory (distance, speed, permanence time in zone etc.)

➤ Specific parameters for Morris Water Maze (latency to target, time near walls, Wishaw’s error, permanence time in quadrants, directionality etc.) ➤ Social interaction (contacts, relative movements etc.) ➤ Immobility periods ➤ Global activity

➤ Rearing (input/output or Triwise option)

➤ Events visualized by the experimenter (using event recorder) ➤ Clockwise and counter clockwise rotations (Triwise option)

SMART is a complete and user-friendly video-tracking system for evaluating behavior in experimental animals. It allows the recording of activity, trajectories, events, social behavior interactions and performs the calculations of a wide range of analysis parameters. The system offers flexible and easy to learn interface for setting up a wide variety of behavioral tests: Water Maze, Open Field, Plus/Radial Arm Mazes, and Place Preference tests in addition to other user-designed applications. SMART works with animals located in up to 16 separate enclosures providing both quantitative and qualitative analysis of each animal’s path. Each animal enclosure can be divided into different zone of interest using the specific tools provided by SMART. Up to 31 different zones (and one Exclusion Zone) can be easily drawn with different name and characteristics (Standard, Target, Arm or Hidden). A special tool for Water Maze is included. Animal trajectories are acquired from real time TV images or videotaped records and stored, enabling you to analyze and reanalyze experiments with different zone configurations and parameters. TRACKING allows not only data acquisition of the spatial position of the animal but also the automatic detection of a range of specific behaviors. Manually scored behaviors (e.g. grooming) can be calculated for any zone or independent variable. The parameters evaluated are presented in reports entirely configurable by the user. The report coverage can be the full track or it can be split into different intervals of time. Results can be directly and automatically exported to Excel®. SMART can elaborate a graphic representation/image of the tracks studied. This option is of great interest to illustrate data in publications and for conferences. An adapted version of SMART, SMART-DT, is provided for free to check data, generate statistics, print out results and obtain graphics. SMARTDT can be installed in as many computers as may be required. The SMART system can be expanded for using the Triwise technology for the automated detection of the head, center-mass and base-tail allowing then a more detailed evaluation of some specific behavioral items — rearing, rotations, object exploration, entries into zones, contacts and more.

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Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Video Tracking

SMART Video-Tracking System for Automated Recording of Animal Behavior (continued) Components Included

Specifications

➤ Cables and connectors

Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM with PCI 32-bit bus master expansion slot available and 1 free USB port. VIA chipset not recommended

Graphic Card

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

System Requirements

Windows® 98, 2000, XP (SP2 or Higher), Vista 32

Sources

Video camera, video tape, DVD player or digital video files

➤ CD and USB protection key ➤ Instruction manual

➤ Free software updates of the acquired system ➤ 2 year warranty on hardware

Options

➤ A wide range of cameras and accessories are available, please contact our technical support staff for details ➤ Material for camera fixation (upon request) ➤ DVD reader/writer

Order # Model

Product

BH2 76-0028 SMART-BS

SMART Video-Tracking System, V 2.5 Single Subject Tracking, Needs FRBOARD

BH2 76-0501 FRBOARD2

Frame Grabber Board (PC Interface Board)

BH2 76-0265 SMART-MA

Multiple Arenas Extension (One Animal Per Arena in up to 16 Arenas)

BH2 76-0266 SMART-SS

➤ Open Field Box, see page 90

Social Behavior Extension (Up to 16 Animals in a Single Arena)

BH2 76-0327 SMART TW

➤ Radial Maze, see page 69

Triwise Module for Detection of Head, Center Mass, and Base-Tail

BH2 76-0267 SMART I/O 8C

Smart System Extension, Control Box for 8 Inputs and 8 Outputs

➤ Black & White Box, see page 92

BH2 76-0268 SMART I/O 32C

Smart System Extension, Control Box for 32 Inputs and 32 Outputs

BH2 76-0269 SMART UPG2.5

Upgrade from previous versions to V 2.5

BH2 76-0270 SMART TS

Telemetric Switch (Remote Start/Stop Switch)

➤ Telemetric switch (remote start/stop switch)

➤ Frame grabber board (PC interface board) ➤ PC station

➤ Multiplexers, digital switches, digital recorder are available upon request

Related Hardware

➤ Circular Pool, see pages 67 – 68 ➤ Elevated Plus Maze, see page 88 ➤ Spatial Place Preference Box, see page 99 ➤ Many other possibilities!

NOTE

We offer a full line of mazes.

Citations Folven KI et al. (2009) Does selenium modify neurobehavioural impacts of developmental methylmercury exposure in mice? Environmental Toxicol. Pharmacol. 28(1):111-119. (motor function, mouse, Norway, New Zeland) Griesbach GS et al. (2009) Controlled contusion injury alters molecular systems associated with cognitive performance. J. Neurosci. Res. 87(3):795-805. (water maze, rat, USA) Handattu SP et al. (2009) Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease. Neurobioly of Disease, 34(3):525534. (water maze, mouse, USA) Harada N et al. (2009) Functional analysis of neurosteroidal oestrogen using gene-disrupted and transgenic mice. J. Neuroendocrinol. 21(4):365-369. (parallelism index, mouse, Japan) Hazane F et al. (2009) Behavioral Perturbations After Prenatal Neurogenesis Disturbance in Female Rat. Neurotoxicity Res. 15(4):1476-3524. (Locomotor activity, rat, France) Lee YK et al. (2009) Protective effect of the ethanol extract of Magnolia officinalis and 4-Omethylhonokiol on scopolamine-induced memory impairment and the inhibition of acetylcholinesterase activity. J. Nat. Med. 63(3):274-282. (water maze, mouse, Korea) Malone DT et al. (2009) Cannabidiol reverses the reduction in social interaction produced by low dose delta9-tetrahydrocannabinol in rats. Pharmacol. Biochem. Behav. 93(2):91-96. (open-field, rat, Australia) Singer HS et al. (2009) Prenatal exposure to antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model. (elevated-plus maze, mouse, USA) Arqué G et al. (2008) Impaired Spatial Learning Strategies and Novel Object Recognition in Mice

OPTIONS

Haploinsufficient for the Dual Specificity Tyrosine-Regulated Kinase-1A (Dyrk1A). PLoS ONE 3(7): e2575. (water maze, mouse Spain) Das SR et al. (2008) Relationship between mRNA expression of splice forms of the _1 subunit of the N-methyl-d-aspartate receptor and spatial memory in aged mice. Brain Research. 1207:142-154. (working memory task, mouse, USA) Fan LW et al. (2008) Alfa-Phenyl-n-tert-butyl-nitrone ameliorates hippocampal injury and improves learning and memory in juvenile rats following neonatal exposure to lipopolysaccharide Eur. J. Neurosci. 27(6): 1475-1484. (open-field, plus-maze, rat, Taiwan) Feiyong Jia et al. (2008) Blocking Histamine H1 improves learning and mnemonic dysfunction in mice with social isolation plus repeated methamphetamine injection. J. Pharmacol. Sci. 107: 167-174. (water maze, mouse, Japan) Hook VYH et al. (2008) Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer’s disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase APP site. J Biochem. Chem. 283(12):7745-53. (water maze, mouse, USA) McClean J et al. (2008) 17_-Estradiol is neuroprotective in male and female rats in a model of early brain injury. Experimental Neurology. 210(1), 41-50. (water maze, rat, USA) Rothstein S et al. (2008) Response to neonatal anesthesia: Effect of sex on anatomical and behavioral outcome. Neuroscience. 152(4):959-969. (rat, USA) Pastor R et al. (2008) Ethanol injected into the hypothalamic arcuate nucleus induces behavioral stimulation in rats: an effect prevented by catalase inhibition and naltrexone. Behavioural Pharmacology. 19(7):698-705. (locomotor activity, rat, Spain) Ruiz-Medina J et al. (2008) Intracranial self-stimulation facilitates a spatial learning and memory task in the Morris water maze. Neuroscience. 154(2): 424-430. (water maze, rat, Spain) Stone EA et al. (2008) An anti-immobility effect of exogenous corticosterone in mice. European Journal of Pharmacology. 580(1-2):135-142. (open-field, Mouse, USA) Younbyoung C et al. (2008) Effect of acupuncture on anxiety-like behavior during nicotine withdrawal and relevant mechanisms. Neuroscience Letters. 430(2): 98-102. (locomotor activity, rat, Republic of Korea)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Video Tracking Smart Junior

Right to the Point Video-Tracking

Components Included Key Features

➤ Simplest video-tracking system available, nine steps and you’re done!

➤ Ready-to-use configurations provide concrete meaningful data

DESIGNED FOR: Water Maze Experiment

➤ Latency to reach the platform and times platform is crossed ➤ Permanence time, distance traveled, speed and number of entries (and %) into zones (platform, pool, quadrants, border and total) ➤ Movement pattern and manually scored events

Open Field Experiment

➤ Permanence time, distance traveled, speed and number of entries (and %) into zones (center, periphery and border) ➤ Movement pattern and manually scored events

Plus Maze Experiment

➤ Permanence time, distance traveled, speed and number of entries (and %) center, open arms and closed arms ➤ Movement pattern and manually scored events

T/Y Maze

➤ Alternations (number, %, max), first arm choice, latency first choice

➤ Permanence time, distance traveled, speed and number of entries (and %) into correct/incorrect arms, left/right arms or A/B/C arms

➤ Free software updates of the acquired system

Options

➤ Telemetric switch (remote start/stop switch) ➤ WebCam or other cameras

➤ PC station or laptop (upon request)

NEW Smart JUNIOR MA Extension! With the NEW MA (Multiple Arenas) extension to Smart JUNIOR, users are able to work with an amazing number of subjects (over a 100!) for maximum efficiency. Create arenas and related zones in less than 10 clicks!. Allows independent or synchronized (all arenas or only selected arenas) start/stop of tracking process. The ONLY system available that features different lighting/contrast and timing control settings for each arena!

Smart JUNIOR

Smart JUNIOR is an economical video-tracking system specially intended for laboratories with very precise interests and needing concise meaningful reports. With a more competitive price, the Smart JUNIOR software fulfills all the basic functions of a classic video-tracking system. Ready-to-use configurations, run panel and data reports are directly targeted to specific standard experiments. An innovative scheduler tool allows managing the subjects and trials in different phases and sessions for an easy retrieval and organization of the final data. Succinct graphs provide a direct visualization of the results obtained in the different experimental groups.

Place Preference

Smart JUNIOR takes advantage of the latest technologies in terms of image processing for providing accurate data in the context of behavioral research. The software platform is expandable: new readyto-use protocol configurations can be easily plugged-in for widening the scope of the system.

➤ Movement pattern and manually scored events

Smart JUNIOR represents the finest solution for completing molecular and cellular studies by standard behavioral analysis. It is also a perfect alternative for labs just beginning behavior studies.

➤ Movement pattern and manually scored events

➤ Permanence time (absolute and relative), distance traveled, speed and number of entries (and %) into compartment associated to drug/placebo and corridor

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➤ Instruction manual

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Video Tracking Smart Junior

Right to the Point Video-Tracking (continued) Related Hardware

➤ Circular Pool, see pages 67 – 68

➤ Elevated Plus Maze, see page 88 ➤ Open Field Box, see page 90

➤ Place Preference, see page 98 ➤ Y or T Maze, by request

Specifications Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

System Requirements

Windows® XP (SP2 or Higher), Vista 32

Images Sources

Webcam, digital video, firewire/USB digital camera; in general, any device compatible with Windows® Image Acquisition (WIA)

Order # Model

Product

BH2 76-0029 SMART JUNIOR Smart Junior Platform (Needs Experiment Modules) BH2 76-0255 SJWM

Water Maze Experiment Module

BH2 76-0256 SJPM

Plus-Maze Experiment Module

BH2 76-0257 SJOF

Open-Field Experiment Module

BH2 76-0416 SJTY

T-Y Maze Experiment Module

BH2 76-0415 SJPP

Place Preference Experiment Module

BH2 76-0508 SJMA

Multiple Arenas Module

BH2 76-0270 Smart Remote

Telemetric Switch

BH2 76-0260 CAMWEB

Logitech Quickcam Express 5000 640x480 30FPS w/Cable USB 1.8 m

BH2 76-0261 CAMWEB2

High Resolution WebCam Creative WebCam NX Ultra 640 x 480 w/Cable USB 1.8 m

BH2 76-0262 CONVANAUSB

Video Converter (Analog/Digital)

OPTIONS

FAQ’s 1. When my trial version expires, what should I do to acquire a license? Just follow the instructions indicated by the Activation Assistant of the Smart JUNIOR and you will get your registered copy within minutes! 2. Once I buy the system, will I have to pay anything else such as annual license or technical/scientific support? Panlab/Harvard Apparatus includes all related expenses in its price. Technical and scientific support is always available for our team. 3. Now there are only 5 Experimental Modules but, do you plan to add new ones? If so, which ones? As long as there are standard experiments with highly standardized parameters to look at, we will not stop widening JUNIOR’S scope. 4. If at a later stage I become interested in a highly sophisticated video tracking system such as your renowned Smart, will I have to pay for a brand new system? At Panlab/Harvard Apparatus we make this transition simple for our customers! What is more, we offer a highly affordable transfer fee for customers wishing to move from Smart JUNIOR to SMART! Contact our technical support staff for more information.

Citation Camarasa J et al. (2008) Memantine prevents the cognitive impairment induced by 3,4methylenedioxymethamphetamine in rats. Eur. J. Pharmacol. 589(1-3):132-9 (open-field, water maze, rats, Spain

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Locomotor Activity & Exploration Guide Locomotor activity refers to the movement from one location to another. In rodents, one of the most important components of exploration, a prominent activity of the animal’s repertoire of spontaneous activity, is locomotion. Moreover, locomotor activity and exploration are involved in many behavioral and physiological functions and are influenced by many external factors, such as environmental conditions (light, temperature, noise) and novelty, and internal factors, such as circadian rhythm, food- or drink-deprivation, prior handling by the researcher, age, gender, strain, and many other factors. Development of behavioral measurements of locomotor activity and exploration was in part relevant in various rodent models as an initial screen for pharmacological effects predictive of therapeutic drug efficacy in humans. Indeed, locomotor and exploration are mediated by neurotransmitters affected by many types of drugs, such as neuroleptic, benzodiazepines, opiates and psychostimulants, and consequently are changed in response to the administration of these drugs. Moreover, alterations of locomotor activity and exploration can have important consequences for paradigms that aim to study more specific processes, such as learning, memory, reward, anxiety and others. Thus, it is imperative to verify if a difference in drug, lesion, strain or genetic manipulation influences general motor activity. Furthermore, locomotor abnormalities are associated with several human diseases such as Parkinson’s and Huntington’s disease or hyperactivity syndrome and are therefore displayed by animal models.

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Locomotor Activity & Exploration Guide Behavioral Test

Behavioral Test

Circadian Locomotor Activity

Open Field Test for Basal Global Activity

Rodents typically display circadian rhythmic variations (defined as a 24-hour rhythm) in behavior and physiology. Circadian global activity is directly assessed in the animal home cage through long periods (>24 hours). The activity parameters (locomotion, exploration, stereotypies) are generally evaluated using automated procedures (ex: photocell beams, video tracking systems, or weight transducers).

Basal locomotor activity is generally assessed in a specific activity arena (can be an open field or other) for short or intermittent periods (<1 hour). Locomotion (horizontal activity), exploration (rearing and object sniffing) and stereotypies (movement without displacement) are then recorded manually or using various automated procedures (photocell beams, videotracking system, or weight transducers).

Reasons for Choosing This Test ➤ No need for habitation; not stressful, familiar environment for the subject ➤ Long-term observation of activity (circadian rhythm) ➤ Easy to perform tests ➤ No animal handling needed ➤ Sensitive for both mice and rats

Related Human Disease/Applications ➤ Drug Screening ➤ Phenotyping ➤ Attention-Deficit Hyperactivity Disorder

Reasons for Choosing This Test ➤ ➤ ➤ ➤ ➤

Free exploration paradigm Widely used in literature Easy to use for inexperienced users Can be entirely automated Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Requires non-stressful conditions (habituation and low lighting conditions)

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤

Drug Screening Phenotyping Parkinson’s Disease Huntington’s Disease Attention-Deficit Hyperactivity Disorder (ADHD)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Locomotor Activity & Exploration Guide Behavioral Test

Behavioral Test

Activity Wheel

Locomotor Response to Novelty

The Rodent Activity Wheel represents a very simple and clever way to register animal physical activity in its home cage environment. The use of this high throughput tool is particularly relevant for research involving circadian rhythms, Phenotyping and drug testing. Typically, the time and distance run on a voluntary running wheel are monitored over several days or weeks to determine whether a particular substance or experimental manipulation has an effect on exercise behavior.

Locomotor response to novelty is an index of animal exploration/anxiety that has been shown to represent a predictive factor for the addictive properties of a drug. In an animal model for vulnerability to drug abuse, animals that exhibit greater motor activity in a novel environment (high responders; HR) are found more sensitive to drugs of abuse and are more likely to self-administer these drugs compared to less reactive animals (low responders, LR). In the light of clinical evidence on comorbiity between drug abuse and mood disorders, this model is widely used to investigate whether individual differences in locomotor reactivity to novelty are related to anxiety and depressionlike responsiveness in rodents.

Reasons for Choosing This Test ➤ Rodent voluntary exercise registering; allows animals to exercise when and at the intensity that they choose ➤ Availability of a running wheel may reduce the effects of chronic stress on depression-like signs in mice ➤ Less labor intensive than treadmill running as researchers need not to be present during wheel running ➤ Relatively inexpensive setup ➤ Ideal for high throughput experiments; many animals can be trained at the same time ➤ Sensitive for both mice and rats

Reasons for Choosing This Test ➤ Explore novelty-seeking behaviors ➤ Free exploration paradigm ➤ Test maximizing avoidance/anxiety related behavior respect to approach/exploratory behavior ➤ Only one exposure (no habituation) and quickly performed ➤ Easy to run ➤ Sensitive for mice and rats

Reasons for Not Choosing This Test

Reasons for Not Choosing This Test

➤ Intensity and duration of the exercise cannot be controlled ➤ Certain lines of transgenic mice may not engage in enough voluntary wheel running exercise to produce training adaptations ➤ Not suitable for studies that require precise timing to explore acute post exercise adaptations (intermittent running throughout the active cycle)

➤ Anxiogenic conditions (novel environment with no possibility of escape)

Related Human Disease/Applications ➤ ➤ ➤ ➤

Drug Screening Phenotyping Addiction Anxiety Disorders

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤

12

Drug Screening Phenotyping Neuromuscular Disease Parkinson’s Disease Muscular Dystrophy

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Locomotor Activity & Exploration Guide Behavioral Test

Behavioral Test

Emergence Test

Novel Object Test

The Emergence Test is a free exploration paradigm designed to reduce anxiety by providing a safe enclosure within the open field in order to assess approach or exploratory behavior in rodents.

The Novel Object Test is a free exploration paradigm that provides animals the opportunity to explore a novel object in a familiar environmental context. Briefly, an object is placed into the center of each open field and the behavior of the animal (time spent exploring the novel object and overall locomotor activity) is registered during a determined period of time.

Briefly, the open field contained a white plastic cylinder with an open end centrally located. The subjects are placed into the cylinder and tested for 10 to 15 minutes. The parameters commonly evaluated in this task are the latency of emergence from the cylinder, the total time spent inside the cylinder, the time spent exploring the cylinder and general locomotor activity.

Reasons for Choosing This Test ➤ Free exploration paradigm in reduced anxiogenic environment ➤ Easy to run ➤ Sensitive for both mice and rats

Related Human Disease/Applications

Reasons for Choosing This Test ➤ Free exploration paradigm in a familiar environment ➤ Test maximizing approach/exploratory behavior respect to avoidance/anxiety-related behavior ➤ Easy to run, even for inexperienced users ➤ Sensitive for both mice and rats

Related Human Disease/Applications ➤ Drug Screening ➤ Phenotyping ➤ Parkinson’s Disease

➤ Drug Screening ➤ Phenotyping ➤ Parkinson’s Disease

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

13


Locomotor Activity & Exploration Guide Behavioral Test

Behavioral Test

Hole Board Test

Treadmill

The Hole Board Test is a specific test for evaluating exploration in rodents. In this test, the animal is placed on an arena with regularly arranged holes on the floor. Both frequency and duration of spontaneous elicited holepoking exploratory behavior are then measured manually or using automated procedures (photocell beams, video tracking system) during a short period of time. Other associated behaviors can also be evaluated, such as grooming, rearing and locomotion.

The Treadmill Test in rodents is a useful tool with a great value in the study of functional capacity and is a validated standard model for investigations in the field of human metabolism. A subject is forced to walk/run on a treadmill (adjustable speed and inclination) during specific periods of time. This test allows the study of various physiological and behavioral functions such as long and short-term effort during exercise, locomotion, metabolic exchanges, cardiac function, motor coordination and fatigue.

Reasons for Choosing This Test

Reasons for Choosing This Test

➤ Allows differentiation between “inquisitive” and “inspective” exploration ➤ Very sensitive to drug effects ➤ Can be completely automated ➤ Easy to use, even for inexperienced users ➤ Sensitive for both mice and rats

➤ Adapted from a human test ➤ Allows the researcher to precisely control the level of exertion ➤ Easy to use, even for inexperienced users ➤ Sensitive for mice and rats

Reasons for Not Choosing This Test Related Human Disease/Applications ➤ Drug Screening ➤ Phenotyping

➤ Needs repetitive daily exposure during few weeks ➤ Requires constant vigilance by the researcher to make sure that the animals run for the entire exercise bout ➤ Use of aversive stimuli to encourage running

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

14

Improvement of sportive human performances Oxidative Stress Diabetes Parkinsons’s Disease Ischemia Ostopenia/Osteoporosis

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Locomotor Activity & Exploration IR Actimeter ActiTrack Tracking Software

Key Features

➤ Interchangeable frames can be used without distinction for rearing activity or poking modes

➤ Can be used without any computer (independent control units) ➤ Dedicated PC optional, not required

Parameters Measured

Options

➤ ActiTrack software, see page 17 ➤ Arena dividers

➤ Hole poke board

➤ Transparent acrylic arena

➤ Fast/Slow activity; i.e. movements with displacement (control unit)

IR Actimeter

➤ Fast/Slow rearings (control unit)

➤ Fast/Slow nose-spoke (control unit)

The Panlab/Harvard Apparatus Infrared (IR) Actimeter allows the study of spontaneous locomotor activity, rearing and optional hole-board test parameters for exploration in rodents. A reliable system for easy and rapid drug screening and phenotype characterization in both day and night lighting conditions.

➤ Intervals of inactivity (ActiTrack)

The system is composed of a two dimensional (X and Y axes) square frame, a frame support and a control unit. Each frame counts with 16 x 16 infrared beams for optimal subject detection.

➤ Fast/Slow stereotypies; i.e. movements without displacement (control unit) ➤ Analysis of animal tracking: distance covered, speed, rearings, permanence time in selected zones, etc. (ActiTrack) ➤ Time in zone (ActiTrack)

➤ Distance travelled (ActiTrack)

➤ Rearing behavior events and duration (ActiTrack)

Components Included

➤ IR unit and control unit with RS-232 communications port ➤ SeDaCom software

➤ Cables and connectors ➤ Instruction manual ➤ Set of spare fuses

➤ 2 year warranty on hardware

The system is completely modular: each frame may be used for evaluation of general activity (one or more animals), locomotor, stereotypic movements, rearings or exploration (nose-spoke detection in the hole-board option). The infrared photocell system can be set with up to 15 levels of sensitivity in order to adapt the frames to the typology of the animal (rats, mice). It can also be set to ignore the beams that are obstructed by objects (e.g. the walls/corners of the home cage). The frames can be controlled by independent control units or directly through SeDaCom computer software, which allows easy exportation of data (through RS-232 serial port) in a format compatible with Excel™. Optionally, the ActiTrack software option may be used to analyze animal trajectories (distance, speed, permanence time in selected zones) and then provide additional complementary data to those obtained using the control units.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

15


Locomotor Activity & Exploration IR Actimeter (continued)

Specifications

Order # Model

Product

System Dimensions:

BH2 76-0121 LE8811

Double IR System, Rats & Mice (Includes LE8825, LE8817, 2 Units LE8815 and SeDaCom)

BH2 76-0122 LE8810

Double IR Activity System, Mice (Includes LE8825, LE8818, 2 Units LE8816 and SeDaCom)

BH2 76-0123 LE8812

Single IR Activity System, Rats (Includes LE8825, LE8817, LE8815 and SeDaCom Software)

BH2 76-0124 LE8809

Single IR Activity System, Mice (Includes LE8825, LE8818, LE8816 and SeDaCom Software)

BH2 76-0125 LE8821

Arena Divider for LE 8815 (Allows Monitoring of 2 Animals at Once)

BH2 76-0126 LE8823

Arena Divider for LE 8816 (Allows Monitoring of 2 Animals at Once)

LE 8811

450 (W) x 450 (D) x 200 (H) mm

LE 8812

220 (W) x 220 (D) x 200 (H) mm

Number of InfraRed Beams Per Frame

32 (16 per axis)

InfraRed Photocells Spacing: LE 8815

25mm

LE 8816

13mm

Material Composition

Aluminum, polypropylene

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000, XP & Vista 32) (if SeDaCom is to be Used)

Maximum Number of Stations

32 InfraRed Frames per computer (either SeDaCom or ActiTrack)

Power Requirements Certifications

BH2 76-0003 ACTITRACK

Enhanced Tracking Software for up to 32 Frames

110/220 V, 50/60 Hz

BH2 76-0127 LE8815

IR FRAME, 450 x 450 mm, 16 x 16 IR Beams

CE compliant

BH2 76-0128 LE8816

IR FRAME, 250 x 250 mm, 16 x 16 IR Beams

BH2 76-0129 LE8814

Transparent Arena 440 x 440 mm (Open Field)

BH2 76-0130 LE8813

Transparent Arena 210 x 210 mm (Open Field)

BH2 76-0131 LE8817

Support for LE 8815 Frames

BH2 76-0132 LE8818

Support for LE 8816 Frames

BH2 76-0133 LE8820

Hole Poke Base for LE 8815 Frame

BH2 76-0134 LE8825

Data Logger (up to 200 Hours Memory) and PC Interface

Citations Canini F et al. (2009) Metyrapone decreases locomotion acutely. Neurosci. Letters. 457(1): 41-44. (locomotion, rat, France) Chetrit J et al. (2009) Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics. PLoS One. 4(7):e6208. (Open-field with Actitrack, rat, France). Lamberty Y et al. (2009) Behavioural phenotyping reveals anxiety-like features of SV2A deficient mice. Behav. Brain Res. 198(2):329-333. (mouse, Belgium) Lopez-Aumatell R et al. (2009) Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat Straits. Behavioural Brain Research, 202: 92-101. (Spontaneous activity, rats, Spain, UK, Switzerland) Tsuchida R et al. (2009) An Antihyperkinetic Action by the Serotonin 1A–Receptor Agonist Osemozotan Co-administered With Psychostimulants or the Non-stimulant Atomoxetine in Mice. J. Pharmacological Sci. 109(3):396-402. (locomotion, mouse, Japan) Goeldner C et al. (2008) Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus. J Neurosci., 28(9):2190 –2198. (object-recognition test, mouse, France) Lalonde R and Strazielle (2008) Exploratory activity and motor coordination in old versus middle-aged C57BL/6J mice. Arch. Gerontol. Geriat. Article in Press (Locomotor activity, mouse, Canada)

16

OPTIONS

Lalonde R and Strazielle (2008) Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice. J: Neurosci. Meth. 171(1):48-52 (Locomotor activity, mouse, Canada) Lalonde R et al. (2008) Effects of a B-vitamin-deficient diet on exploratory activity, motor coordination, and spatial learning in young adult Balb/c mice. Brain Res. 1188:122-131 (open field, mouse, Canada) Goeldner C et al. (2008) Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus. J Neurosci., 28(9):2190 –2198. (object-recognition test, mouse, France) Rubio M (2008) CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology. 54(6):976988. (rat, Spain, USA) Belujon P et al (2007) Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats. J Neurosci. 27(36):9595-9606. (Parkison rats, France) Sonnier L et al. (2007) Progressive loss of dopaminergic neurons in the ventral midbrain of adult mice heterozygote for Engrailed1. J Neurosci. 27(5): 1063-1071. (mouse, France)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Locomotor Activity & Exploration ActiTrack Software for IR Actimeter

software species is hardware specific

Specifications

Key Features

Computer Requirements

➤ Control up to 32 frames

2.2 GHz Processor or higher (Celeron processor excluded), 2 Gb of RAM

➤ Provides spatial position, pattern of displacement and rearings

System Requirements

Windows® XP compatible operating system (SP2 or higher), Vista 32

➤ User-adjustable thresholds for classifying activity into fast, slow and resting movements

Order # Model

Product

BH2 76-0003 ActiTrack

Tracking Software for up to 32 IR Frames

➤ Allows track re-analysis with an unlimited number of user-defined zones

➤ Enables re-playing experiment using different threshold for movement speed definition

➤ Can be installed in as many computers as may be required for track analysis

Parameters Measured

➤ Traveled distance (and % ) into user-defined zones ➤ Maximum, minimum and mean speed

➤ Time (and %) moving fast, slow and resting

➤ Permanence time (and %) into user-defined zones ➤ Number of entrances into user-defined zones ➤ Number and mean duration of rearings

➤ Number of clockwise and counter-clockwise turns ➤ Track history analysis

Components Included

➤ Software CD with USB protection key ➤ Instruction manual

➤ Free software updates of the acquired system (excluding UPGRADES)

Citations Chetrit J et al. (2009) Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics. PLoS One. 4(7):e6208. (Open-field with Actitrack, rat, France). Lamberty Y et al. (2009) Behavioural phenotyping reveals anxiety-like features of SV2A deficient mice. Behav. Brain Res. 198(2):329-333. (mouse, Belgium) Tsuchida R et al. (2009) An Antihyperkinetic Action by the Serotonin 1A–Receptor Agonist Osemozotan Co-administered With Psychostimulants or the Non-stimulant Atomoxetine in Mice. J. Pharmacological Sci. 109(3):396-402. (locomotion, mouse, Japan) Goeldner C et al. (2008) Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus. J Neurosci., 28(9):2190 –2198. (object-recognition test, mouse, France) Rubio M (2008) CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology. 54(6):976988 (rat, Spain, USA) Reiss D et al (2007) Effects of social crowding on emotionality and expression of hippocampal nociceptin/orphanin FQ system transcripts in mice. Behav. Brain Res. 184(2):167-173 (mouse, France) Sonnier L et al. (2007) Progressive loss of dopaminergic neurons in the ventral midbrain of adult mice heterozygote for Engrailed1. J Neurosci. 27(5): 1063-1071. (mouse, France) Kucerova J et al. (2006) Gender differences in cannabinoid and ecstasy interacting effects in mice. Homeostasis in health and diseases. 2006(1-2): 95-96. (mouse, Czech Republic) Menendez J et al. (2006) Suppression of Parkin enhances nigrostriatal and motor neuron lesion in mice over-expressing human-mutated tau protein. Human Molecular Genetics. 15(13): 20452058. (mouse, Spain) Tanaka et al. (2006) Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits in Adcyap1-Deficient Mice. J. Neurosci. 26(19): 5091-5097. (mouse, Japan)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

17


Sensory Motor & Coordination Guide Assessment of sensory motor and coordination is an important part of behavioral studies. Behaviors result from the integration of environmental sensory stimuli and their conversion within the central nervous system into motor commands.

The notion of brain-body-environment interaction refers to causal effects. Simplistically, sensory inputs causally affect motor outputs, and these motor outputs in turn causally affect sensory inputs. Such “perception-action loops” is crucial to any biological organism or artificial system that possesses the ability to react to the environment. Integration of the sensory perception and motor output occurs in the cerebellum and the basal ganglia. Both structures project by many neural pathways to the motor cortex, which commands movements to the muscles, and to the spinocerebellar tract, which provides feedback on the position of the body in space (proprioception). Consequently, cerebellum and basal ganglia are responsible of smooth, coordinated movements and a disturbance of either system will show up as disorders in fine movements, equilibrium, posture, and motor learning, as observed in Parkinson’s or Huntington’s diseases. Studying neurobiological mechanisms of these common diseases is therefore essential to find efficient therapeutic strategies. To do so, various behavioral tasks have been developed in laboratory rodent models and are largely validated. Moreover, because behavioral experiments typically measure motor coordinated responses to sensory information, assessment of these abilities is required for the interpretation of results of experiments designed to assess other neurobiological processes.

18


Sensory Motor & Coordination Guide Behavioral Test

Behavioral Test

Rota Rod Test

Grip Strength Test

The Rota Rod is a standard test of motor coordination, balance and fatigue in rodents. The animals are placed on moving lanes rotating at different speeds or under continuous acceleration, and the time latency to fall from the Rota Rod is recorded.

The purpose of this test is to evaluate the limb motor or muscular functions in rodents. It represents a complementary test to the Rota Rod. Subjects are pulled by the tail while they are allowed to grasp a grid or a bar. The maximum force applied to the grid or the bar just before they lose grip is recorded.

Reasons for Choosing This Test ➤ ➤ ➤ ➤

Easy to perform test Allows multi-animals sessions Allows evolution curves of performance Sensitive for both rats and mice

Reasons for Choosing This Test ➤ Easy and rapid test ➤ Sensitive for both rats and mice

Reasons for Not Choosing This Test Reasons for Not Choosing This Test ➤ Poor in detecting minor deficits or improvements in coordination ➤ Needs habituation sessions

➤ High variability in the response ➤ Habituation to the response inducing a loss of motivation when measurements are performed at short interval ➤ Influenced by user handling (need training)

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

Motor Phenotyping Drug Screening Parkinson’s Disease Huntington’s Disease Alcohol Dependence Aging

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

Neuromuscular Diseases Phenotyping Drug Screening Parkinson’s Disease Huntington’s Disease Aging

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

19


Locomotor Activity & Exploration Guide Behavioral Test

Behavioral Test

Startle Response to Acoustic and Tactile Stimulus

Prepulse Inhibition of Startle Reflex

The startle response is a brainstem reflex elicited by an unexpected acoustic or tactile stimulus. The evaluation of startle reflex response (and its habituation) to acoustic or tactile stimulus of different intensities is widely used for the detection of sensorimotor gating and hearing deficiencies in phenotyping evaluations.

Prepulse Inhibition (PPI) paradigm is commonly used to evaluate sensorimotor gating as well as attentional processes involved in information selection processing. The startle response is a brainstem reflex elicited by an unexpected acoustic or tactile stimulus. In the prepulse inhibition test, sensorimotor gating is assessed by evaluating the characteristics of the innate reduction of the startle reflex induced by a weak prestimulus. This test measures pre-attentive processes that operate outside of conscious awareness and is widely used in animal models of diseases marked by an inability to inhibit, or “gate” irrelevant information in sensory, motor, or cognitive domains.

Reasons for Choosing This Test ➤ Neurological phenotyping for motor and sensory capabilities ➤ Objective measurement: automated detection of startle reflex ➤ Sensitive for both rats and mice

Reasons for Not Choosing This Test

Reasons for Choosing This Test

➤ Restraint conditions (habituation phase needed) ➤ Non-specific influence of attention processes

➤ Reproduces the same paradigm used in humans to detect attentional and sensorimotor gating disorders ➤ Objective measurement: automated detection of startle reflex ➤ Sensitive for both rats and mice

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

Neurological Phenotyping Hyperekplexia Auditory Deficits Parkinson’s Disease Huntington’s Disease Schizophrenia

Reasons for Not Choosing This Test ➤ Restraint conditions (habituation phase needed) ➤ Influenced by non-specific effects on sensorimotor gating

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤

20

Drug Screening Phenotyping Attention-Deficit Hyperactivity Disorder (ADHD) Schizophrenia Autism Obsessive Compulsive Disorder Huntington’s Disease Nocturnal Enuresis Tourette’s Syndrome

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Sensory Motor & Coordination Guide Behavioral Test

Behavioral Test

Rotameter Test

Activity Wheel

Rotational behavior has proved a popular technique for screening the behavioral effects of a wide variety of lesions, drugs, and other experimental manipulations on the brain of rodents. This test is widely carried out in experiments using animal models of Parkinson disease with unilateral lesions in the dopaminergic nigrostriatal system in which the number and direction of animal rotations in quantified after apormorphine treatment.

The Rodent Activity Wheel represents a very simple and clever way to register animal physical activity in its home cage environment. The use of this high throughput tool is particularly relevant for research involving circadian rhythms, phenotyping and drug testing. The time and distance run on a voluntary running wheel are monitored over several days or weeks to determine whether a particular substance or experimental manipulation has an effect on exercise behavior.

Reasons for Choosing This Test Reasons for Choosing This Test

➤ Rapid and easy-to-do test ➤ Can be entirely automated

Related Human Disease/Applications ➤ Drug Screening ➤ Parkinson’s Disease

Behavioral Test

Treadmill The Treadmill Test in rodents is a useful tool with a great value in the study of functional capacity. It is a validated standard model for investigations in the field of human metabolism. A subject is forced to walk/run on a treadmill (adjustable speed and inclination) during specific periods of time. This test allows the study of various physiological and behavioral functions such as long and short-term effort during exercise, locomotion, metabolic exchanges, cardiac function, motor coordination and fatigue.

➤ Rodent voluntary exercise registering; allows animals to exercise when and at the intensity that they choose ➤ Accessibility to running wheel may reduce the effects of chronic stress on depression-like signs in mice ➤ Less labor intensive than treadmill running as researchers need not to be present during wheel running ➤ Relatively inexpensive setup ➤ Ideal for high throughput experiments; many animals can be trained at the same time ➤ Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Intensity and duration of the exercise cannot be controlled ➤ Certain lines of transgenic mice may not engage in enough voluntary wheel running exercise to produce training adaptations ➤ Not suitable for studies that require precise timing to explore acute post exercise adaptations (intermittent running throughout the active cycle)

Reasons for Choosing This Test ➤ Adapted from a human test ➤ Allows the researcher to precisely control the level of exertion ➤ Easy to use, even for inexperienced users ➤ Sensitive for mice and rats

Reasons for Not Choosing This Test ➤ Needs repetitive daily exposure lasting several weeks ➤ Requires constant vigilance by the researcher to make sure that the animals run for the entire exercise test time ➤ Use of aversive stimuli to encourage running

Related Human Disease/Applications ➤ ‰ ‰ ‰ ‰

Drug Screening Phenotyping Neuromuscular Disease Parkinson’s Disease Muscular Dystrophy

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

Improvement of sportive human performances Oxidative Stress Diabetes Parkinsons’s Disease Ischemia Ostopenia/Osteoporosis

21


Sensory & Motor

Rota Rod for Motor Coordination in Rodents The animal is placed on the roller lane of the Rota Rod and the timer is started. When the animal drops safely into its own lane, the time latency to fall (minutes and seconds) and rotation speed are automatically recorded. A removable upper separator for rat models is included to prevent interference between animals running in adjacent lanes.

Rota Rod

The Rota Rod is controlled by an advanced microprocessor which provides precise timing control and ultra-accurate speed regulation. Rotation can be electronically set at a constant speed (4-40 rpm) using a dial on the front panel. Alternatively, acceleration rate may be selected at a defined time (30 sec., 1, 2, 5 or 10 min). Acquired data is saved in the form of a table-lanes/trials. The Panlab/Harvard Apparatus Rota Rod is also provided with a computer interface enabling easy exportation of data through RS-232 serial port in a format that is compatible with Excel™.

Specifications Key Features

➤ Combined Rota Rod for mice and rats available! ➤ Mechanical detection of fall ➤ Individual lane timers

➤ Constant speed and fixed acceleration rate modes

➤ Automatic recording of latencies to fall and rotation speed ➤ Memory for storing data

➤ Data Transfer software included (SeDaCom)

Parameters Measured ➤ Animal latency to fall

➤ Rotation speed when fall occurs

Components Included

➤ Rota Rod unit with integrated control unit and RS-232 communication’s port

362 (W) x 240 (D) x 400 (H) mm

Extra Hood

100 (H) mm

Lane and Rod Dimensions-Rats

75 mm (W); 60 mm rod diameter

Lane and Rod Dimensions-Mice

50 mm (W); 30 mm rod diameter

Material Composition

Methacrylate, arnite (lanes)

Constant Speeds

4-40 RPM

Acceleration Rate

30 seconds, 1, 2, 5, or 10 minutes

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000, XP & Vista 32)

Maximum Number of Stations

1 per computer (multiple set-ups also available under request)

Certifications

CE compliant

Power Requirements

110/220 V, 50/60 Hz

Order # Model

Product

➤ Extension hood for rats (only for LE8300 and LE8500)

BH2 76-0237 LE 8200

➤ SeDaCom software

Accelerating Rota Rod for 5 Mice Including SeDaCom Software

➤ Cables and connectors

BH2 76-0238 LE 8300

➤ Certificate of calibration

Accelerating Rota Rod for 4 rats Including SeDaCom Software

➤ Instruction manual

BH2 76-0239 LE 8500

➤ Set of spare fuses

OPTIONS

Accelerating Rota Rod for 4 Rats or 4 Mice Including SeDaCom Software

Options

BH2 76-0114 LE 7000

➤ Cylinder for mice, rats or both depending on the model

➤ 2 year warranty

➤ LE7000 thermal printer

Rota Rod The Panlab/Harvard Apparatus Rota Rod provides an easy way to test the effects of drugs, brain damage, or diseases on motor coordination or fatigue resistance in rodents.

22

Unit Dimensions

Thermal Printer

Citations Favre-Guilmard C et al. (2009) Different antinociceptive effects of botulinum toxin type A in inflammatory and peripheral polyneuropathic rat models . Eur. J. Phar. 617(1-3): 48-53 (rat, France) Marino P et al. (2009) A polysialic acid mimetic peptide promotes functional recovery in a mouse model of spinal cord injury. Exp Neurology, 219(1):163-174. (spinal cord injury, mouse, France) Viosca J et al. (2009) Germline expression of H-RasG12V causes neurological deficits associated to Costello syndrome. Genes, Brain and Behav. 8(1):60-71. (mouse, France) Favre-Guilmard C et al. (2008) The novel inhibitor of the heterotrimeric G-protein complex, BIM-46187, elicits anti-hyperalgesic properties and synergizes with morphine. Eur. J. Phar. 594(1-3): 70-76 (rat, France) Korhonen L et al. (2008) Expression of X-chromosome linked inhibitor of apoptosis protein in mature purkinje cells and in retinal bipolar cells in transgenic mice induces neurodegeneration. Neuroscience 156(3):515-526 (LE8200, mouse, Finland)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Sensory & Motor

Grip Strength Meter for Evaluation of Muscular Strength Grip Strength Meter The grip strength meter allows the study of neuromuscular functions in rodents by determining the maximum force displayed by an animal. This test is included in the Functional Observational Battery (FOB) to screen for neurobehavioral toxicity. In this context, changes in grip strength are interpreted as evidence of motor neurotoxicity. The grip strength meter is positioned horizontally and the subjects are held by the tail and lowered towards the apparatus. The animals are allowed to grasp the metal grid or T-bar and are then pulled backwards in the horizontal plane. The force applied to the grid or to the bar just before it loses grip is recorded as the peak tension. This force can be measured in kilograms, grams, pounds or Newtons. Data output is carried out through RS-232, printer, or chart recorder. Depending on the grid type used, grip strength can be measured from the front or hind paws.

Specifications

Grip Test Accessories

Bar for Rat

Bar for Mouse

(for front or rear paws)

(for front or rear paws)

Grid for Mouse Grid for Rats (for four paws)

(for front paws & four paws)

Key Features

➤ Stand alone system, PC optional, not required

➤ Fits to rats and mice with a simple change of grip accessories ➤ Multi-units display: kgs, grams, lbs., Newtons

➤ New and unique internal computations allows direct reading of average value, standard deviation and variability for subjects and up to 100 animals

Parameters Measured

➤ Maximum force developed by the front and hind paws

Components Included

➤ Display unit with RS-232 connection for PC ➤ Metal stand

➤ Grid or bar (one or two grids/bar) ➤ Instruction manual ➤ 1 year warranty

Options

➤ RS-232 cable

➤ RSIC software

➤ Additional grid/bar

➤ Statistical impact printer with cable

Dimensions of 2 Grid System

750 (W) x 180 (D) x 200 (H) mm

Sensor Capacity

0-2 kG (20N)

Sampling Speed

1000 Hz

Measurement Range

0 to 2000 grams

Resolution

0.1 gram

Accuracy

0.2 % of full scale

Material Composition

Stainless steel (Grid)

Power Supply

110 V/220 V

Dimensions of Single System

400 (W) x 180 (D) x 200 (H) mm

Order # Model

Product

BH2 76-0483 BSBIOGS3

Grip Strength Test Complete with 1 Accessory, 110 or 220 Volts

BH2 76-0484 BSBIORSIC

Data Acquisition RSIC Software Windows® XP (Dongle and CD)

BH2 76-0485 BSBIOAGRS232 RS-232 Cable BH2 76-0479 BSBIOGRIPBR

Bar for Rats (Front Paws)

BH2 76-0480 BSBIOGRIPBS

Bar for Mice (Front or Rear Paws)

BH2 76-0481 BSBIOGRIPGR

Grid for Rats (Front or Four Paws)

BH2 76-0482 BSBIOGRIPGS

Grid for Mice (Front & Four paws)

Citations Dudra-Jastrzebska et al. (2009) Pharmacodynamic and pharmacokinetic interaction profiles of levetiracetam in combination with gabapentin, tiagabine and vigabatrin in the mouse pentylenetetrazole-induced seizure model: An isobolographic analysis. Eur. J. Pharmacol. 605(1-3): 87-94. (mouse, Poland, UK) Dupuis L et al. (2009) Muscle Mitochondrial Uncoupling Dismantles Neuromuscular Junction and Triggers Distal Degeneration of Motor Neurons. PLoS ONE 4(4):e5390. (mouse, France) Kozinska J et al (2009) Spironolactone potentiates the protective action of some selected antiepileptic drugs against maximal electroshock-induced seizures in mice. Annales UMCS, Pharmacia. 22(1):123134. (mouse, Poland) Lambertsen KL et al. (2009) Microglia Protect Neurons against Ischemia by Synthesis of Tumor Necrosis Factor. J. Neurosci. 29(5):1319-1330. (BIO-GT3, mouse, Denmark, Sweden). Luszczki JJ et al. (2009) N-(anilinomethyl)-p-isopropoxyphenylsuccinimide potentiates the anticonvulsant action of phenobarbital and valproate in the mouse maximal electroshock-induced seizure model Neurosci. Res. 64(3):267-272. (mouse, Poland, Armenia) Akhtar M et al. (2008) Effect of thioperamide on oxidative stress markers in middle cerebral artery occlusion model of focal cerebral ischemia in rats. Human & Experimental Toxicology. 27(10):761-767. (rat, India)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

23


Sensory & Motor Grip-Strength Meter

Peak Preamplifier Both the Grip Strength Meter for Rats and the model for Mice are used with this Peak Amplifier. It automatically discriminates whether the grip force is generated by the rat and mouse transducer and expresses them in grams and in decimal of grams respectively. The data supplied by the peak amplifier is available in digital and analog form. The waveform of the pull can be externally recorded, for example via a channel recorder or the signal may be taken to a data acquisition system.

Grip-Strength Meter is Supplied Complete with the Following Components

Grip-Strength Meter This system measures the force that is required to make a mouse or rat release its grip. It is ideal to measure the effects of drugs, toxins, muscle relaxants, disease, aging or neural damage on muscle strength. The rat or mouse is placed over a Perspex plate, in front of a grasping bar, either T-shaped or trapeze-shaped. Rodents instinctively grab anything they can to try to stop this involuntary backward movement. The will continue to grip the trapeze until the pulling force overcomes their grip strength. After the animal loses its grip, the peak preamplifier automatically stores the peak pull force and shows it on a liquid crystal display. The sensor mechanism is a T-shaped or trapeze-shaped bar whose height is adjustable. The bar is fitted to a force transducer connected to the Peak Amplifier. The Mouse unit is similar to the rat model except the grasping trapeze is proportionately sized for mice and the transducer sensitivity is adjusted to measure the grip strength of mice.

Peak Amplifier, incorporating a digital display

Force Transducer Suitable for Either Rats or Mice

Trapezes for Either Rats or Mice, T-shaped bar for Either Rats or Mice

Perspex Plate with 10 mm diameter upright

Open-Side Boss Head

Table Clamp

Mains Cable

Set of 2 fuses for either 115 V or 230 V operation

Instruction Manual

Order # Model

Product

BH2 72-6713 47105/115 V

Grip-Strength Meter for Rats, 115 V/230 V

BH2 72-6715 47106/115 V

Grip-Strength Meter for Mice, 115 V/230 V

BH2 72-6717 47105-002

Force Transducer Assembly for Rat

BH2 72-6718 47105-003

Force Transducer Assembly for Mouse

BH2 72-6719 47105-004

Pespex Plate with 10 mm Diameter Upright

BH2 72-6723 47105-323

Table Clamp

BH2 72-6725 4003

Open-Side Boss Head

REPLACEMENT PARTS

A complete system is comprised of the follow components: 1. A base plate of black sand-blasted Perspex, complete with upright and open-side boss-head 2. A grasping-bar (a grasping trapeze is also supplied) 3. A force transducer of adjustable height, provided with connection cable and connector to the peak amplifier 4. A peak amplifier

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Sensory & Motor Rodent Activity Wheel Activity Wheel and Cage

Key Features

➤ Easy way to quantify rodent voluntary exercise in their home cage environment ➤ Preserves animal living space

➤ Stainless steel wheel construction ➤ For rat, mice and hamsters

➤ Ideal for high throughput experiments

Applications

➤ Activity - circadian rhythms, exercise

➤ Cognition - environmental enrichment

➤ Disease models - Huntington’s, Attention-Deficit Hyperactivity Disorder, Addiction, Anorexia and more

Rodent Activity Wheel The Rodent Activity Wheel represents a very simple and clever way to register animal voluntary physical activity in its home cage environment. The use of this high throughput tool is particularly relevant for research involving circadian rhythms, phenotyping and drug testing. The animals are housed individually in the home cages equipped with the running wheel.

All the components of the wheel assembly (wheel, wheel hub and support) are made of stainless steel and are used with standard ACE (Allentown Caging Equipment) polycarbonate rodent cages provided with its wire lid. The wheel is mounted outside the home cage to preserve animal living space. All non-electrical cage components are autoclavable.

Specifications Model

Ø Wheel

Lane Width

ACE* Cage Size

LE904

36 cm

10 cm

42 (W) x 26 (D) x 19 (H) cm

LE905

16 cm

6 cm

36 (W) x 20 (D) x 14 (H) cm

* Other brands are available under request

Order # Model

Product

BH2 76-0412 LE904

Activity Wheel and Cage, Rat

BH2 76-0413 LE905

Activity Wheel and Cage, Mouse

BH2 76-0414 LE907

Single Wheel Counter

BH2 76-0243 LE3806

Multi-Counter (up to 30 wheels) including SedaCom PC interface

OPTIONS

The total number of wheel rotation made by the animal is displayed on the external LE907 individual counter or LE3806 multi-counter devices. LE3806 multi-counter allows storing the data in user-defined time intervals and exports them to the SeDaCom PC interface (through RS232 serial port) in a format compatible with Excel™.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

25


Sensory & Motor

Rodent Activity Wheel and Cage BH2 60-1943 Rodent Activity Wheel and Cage shown complete with Water Bottle, Waste Tray, Support Stand and Counter (not included)

The clear polycarbonate cage has glass-like clarity and excellent impact strength. The cut-out bottom allows changing of bedding and removal of excreta without disturbing the animal. (Meets NIH floor space requirements for a single rodent). A solid stainless steel lid covers the opening at the edge of the Activity Wheel while a wire lid with exclusive lid locks fasten securely to the cage body. These lids prevent the animal from escaping. The wire lid incorporates a water bottle support with rubber stopper guard and a U-shaped food hopper for pellets.

Specifications Dimensions: Overall, H x W x D

36.4 x 26.8 x 50 cm (14.25 x 10.375 x 19.5 in)

Wheel, OD x W

34.5 x 9 cm (13.5 x 3.5 in)

Floor Area: Cage

929 cm2 (144 in2)

Cage with Wheel

516 cm2 (80 in2)

Order # Product FOR RATS

BH2 60-1943 Rat Activity Wheel and Cage BH2 60-1944 Polycarbonate Waste Tray Collects Excreta, H x W x D, 3.5 x 28 x 45 cm (1.375 x 11.125 x 17.5 in); Requires Use of BH2 60-1945 Support Stand, see below, pkg. of 1 BH2 60-1945 Support Stand for Cage and Waste Tray for Rat Cage, Stainless Steel, Supports One Activity Cage with Wheel and Waste Tray; Allows Removal of Waste Tray without Disturbing the Cage or Animal

➤ Easy measurement of rodent activity ➤ For mice, rats and hamsters

➤ All stainless steel wheel construction

➤ Clear polycarbonate cage for visibility and strength

Rodent Activity Wheel

This Rodent Activity Wheel provides an easy, convenient method for measuring lab rodents’ physical activity in response to chemical or environmental stimuli. It is especially useful for research involving circadian rhythms or pharmaceutical testing. The Rodent Activity Wheel and Cage package comes complete with: stainless steel activity wheel, wheel hub and support, sheet and activity wire lids and polycarbonate cage with cut away bottom and stainless steel floor grid. The Activity Wheel allows the animal to exercise voluntarily. It has long-lasting, low-friction Teflon TFE bushings for quiet, smooth action. The stainless steel hub and support rod provide strength and durability and the wide wheel allows small to large animals to exercise. A magnetic switch with LCD counter is available as an accessory for recording animal activity on the wheel, counted as wheel revolutions. The magnetic switch can be used with both the rat and mouse wheels.

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BH2 60-0506 Polycarbonate Water Bottle for Rat Cage, 500 ml Glass Clear and Shatterproof. Extremely Rugged. Permanent, Molded-in Graduations for Easy Measurement. Complete with Chew-Proof Type 316 SS Cap and Sipper tube. Exclusive 1.8 mm Sipper Tube Opening Minimizes Spontaneous Dripping BH2 60-1946 Magnetic Switch with LCD Counter the Magnetic Switch Counts Whole Revolutions of the Activity Wheel. Operates on an ExtendedLife Battery (Included). A Safety Lock Position on the Reset Button Helps Eliminate Accidental Resettings. Assembly Required to Connect Unit to the Activity Wheel and Cage. Works with Both Rat and Mouse Wheel.

FOR MICE

BH2 60-2429 Mouse Activity Wheel and Cage BH2 60-2425 Polycarbonate Waste Tray for Mouse Cage BH2 60-2423 Support Stand for Cage and Waste Tray for Mouse Cage BH2 60-2424 Polycarbonate Water Bottle for Mouse Cage BH2 60-1946 Magnetic Switch with LCD Counter, see Description Above

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Sensory & Motor Small Animal Treadmill Treadmill Unit with RS-232 Communication Port

Treadmills Key Features

➤ Silent operation, even at high speeds ➤ Accurate control of shock intensity

➤ Data acquisition software included (SeDaCom) ➤ Positive/Negative slope

➤ High performance motor ➤ Easy to clean

Parameters Measured ➤ Total distance covered

➤ Distance covered at each moment

➤ Accumulated shock time per animal

➤ Number of contacts with the shock grid

Components Included

➤ Treadmill unit with RS-232 port ➤ Allen key

➤ SeDaCom software

➤ Cables and connectors ➤ Instruction manual ➤ Set of spare fuses ➤ 2 year warranty

Options

➤ LE7000 thermal printer

Panlab/Harvard Apparatus treadmills are rolling belts with an adjustable speed and slope, enabling forced exercise training and accurate testing of fatigue in rodents. Different models are available depending on the user’s needs from one to five lanes. These treadmills have an adjustable speed (up to 150 cm/s) and slope (from -25 to +25 degrees) and a control unit. The rolling belt is built with specially selected materials to guarantee the best performance under conditions of intensive use and requires minimum maintenance. It is also designed with simplicity for keeping it clean. The lanes (corridors of activity for the animal) have sufficient width for the subject to correct its errors in coordination, thereby allowing an exact measurement of the fatigue without deficiencies in motor coordination. The unit controls the speed of the belt, shows measured data in its display, provides current to the shocking grid and allows communication with the PC for data storage, via the RS-232 output and SeDaCom software. Belt velocity can also be controlled by software. Parameters measured in a trial are: belt speed and slope, distance travelled, shock time, and shock intensity. The electrical shock supplied by the grid is of constant intensity (from 0 to 2 mA), that is, the current which circulates through the animal (and therefore its effect) only depends on the value of the mA chosen and not of the subject (quantity of body mass in contact with the bars, perspiration, etc.) The apparatus can optionally be provided with an air isolated enclosure for respiratory metabolism studies - single lane versions only. Gas analyzer, air supply and switching units as well as software must be purchased separately for use with air tight option.

➤ LE87XXCO air tight option for calorimetry studies (available only on single lane models) Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

27


Sensory & Motor

Small Animal Treadmill (continued) Specifications Current Range

Adjustable from 0 to 2 mA

Belt Speed

Adjustable from 5 to 150cm/sec

Running Surface

450 mm long x 100 mm wide

Running Lanes

1, 2, or 5, depending upon model selected

Shock Grid

190 mm long x 100 mm wide

Slope Adjusment

From 0° to 25° (negative slope also available upon request)

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000, XP & Vista 32)

Maximum Number

1 per computer with SeDaCom up to 10 units of Stations

Certifications

CE compliant

Power Requirements

110V or 220V, 50/60Hz

Order # Model

Product

BH2 76-0303 LE8700

Rat Single Lane Treadmill Including Shock Source and SeDaCom Software

BH2 76-0304 LE8708

Mice Single Lane Treadmill Including Shock Source and SeDaCom Software

BH2 76-0305 LE8715

Rabbit Single Lane Treadmill Including Shock Source and SeDaCom Software

BH2 76-0306 LE8706

Rat Double Lane Treadmill Including Shock Source and SeDaCom Software

BH2 76-0307 LE8709

Mice Double Lane Treadmill Including Shock Source and SeDaCom Software

BH2 76-0308 LE8710R

5 Lanes Treadmill for Rats, Including Shock Source and SeDaCom Software

BH2 76-0309 LE8710M

5 Lanes Treadmill for Mice, Including Shock Source and SeDaCom Software

OPTIONS

28

BH2 76-0310 LE 87XXCO

CO Air Tight Option (Only Available for LE8700, LE8708 and LE8715)

BH2 76-0114 LE 7000

Thermal Printer

BH2 76-0312 LE8740R

LE8710 Lead for Rats

BH2 76-0313 LE8740M

LE8710 Lead for Mice

BH2 76-0314 LE8730R

LE8710 Grid for Rats

BH2 76-0315 LE8730M

LE8710 Grid for Mice

Citations Caron AZ et al. (2009) A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse. J. Appl. Physiol. 106: 2049-2059. (mouse, Canada) Casas F et al. (2009) Overexpression of the Mitochondrial T3 Receptor Induces Skeletal Muscle Atrophy during Aging. PLoS ONE. 4(5):e5631. (mouse, Spain, France) Hoffman-Goetz L et al. (2009) Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-_ in intestinal lymphocytes. Brain, Behav. Immunity. 23(4):498-506. (mouse, Canada) Jiao Q et al. (2009) Sarcalumenin is Essential for Maintaining Cardiac Function During Endurance Exercise Training. Am. J.Physiol. Heart Circ. Physiol. (mouse, Japan) In Press. Macambira SG et al. (2009) Granulocyte colony-stimulating factor treatment in chronic Chagas disease: preservation and improvement of cardiac structure and function. FASEB J. In Press. (LE8700, mouse, Brazil) Yoshida M et al. (2009) Functional evaluation of pallid mice with genetic emphysema. Laboratory Investigation. 89(7):760-768. (LE8709, mouse, Japan) Cassano M et al. (2008) Magic-Factor 1, a Partial Agonist of Met, Induces Muscle Hypertrophy by Protecting Myogenic Progenitors from Apoptosis. PLoS ONE. 3(9):e3223 (mouse, Italy) Ferrara N et al. (2008) Exercice training promotes SIRT1 activity in aged rats. Rejuvenation Res. 11(1):139-150 (rat, Italy) Knauf C et al. (2008) Brain Glucagon-Like Peptide 1 Signaling Controls the Onset of High-Fat DietInduced Insulin Resistance and Reduces Energy Expenditure. Endocrinology. 149(1):4768-4777 (mouse, France) Marques E et al. (2008) Influence of chronic exercise on the amphetamine-induced Dopamine Release and Neurodegeneration in the Striatum of the Rat. Ann. N. Y. Acad. Sci. 1139:222-231. (LE8706, rat, Portugal) Knauf C et al. (2008) Brain Glucagon-Like Peptide 1 Signaling Controls the Onset of High-Fat DietInduced Insulin Resistance and Reduces Energy Expenditure. Endocrinology. 149(1):4768-4777 (mouse, France) Cassano M et al. (2008) Magic-Factor 1, a Partial Agonist of Met, Induces Muscle Hypertrophy by Protecting Myogenic Progenitors from Apoptosis. PLoS ONE. 3(9):e3223 (mouse, Italy) Ferrara N et al. (2008) Exercice training promotes SIRT1 activity in aged rats. Rejuvenation Res. 11(1):139-150 (rat, Italy) Serradj N and Jamon M (2007) Age-related changes in the motricity of the inbred mice strains 129/sv and C57BL/6j. Behavioral Brain research 177(1): 80-89. (mouse, France) Suelves M et al. (2007) uPA deficiency exacerbates muscular dystrophy in MDX mice. The Journal of Cell Biology 178(6):1039-51. (Mouse, Spain) Alonso M et al. (2006) Melatonin inhibits the expression of the inducible isoform of nitric oxide synthase and nuclear factor kappa B activation in rat skeletal muscle. J. Pineal Res. In Press Billat V et al. (2005) Inter- and intrastrain variation in mouse critical running speed. J. Apll. Physiol. 98: 1258-1263. (mice, France). Majczynski H et al. (2005) Serotonin-Related Enhancement of Recovery of Hind Limb Motor Functions in Spinal Rats after Grafting of Embryonic Raphe Nuclei. J. Neurotrauma. 22(5): 590-604. (Rat, Poland)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Sensory & Motor

Rotameter for Evaluating Rotation Behavior A bi-directional rotation sensor provides a double (right and left turns) output with adjustable regulation of pulses/turns (between 3 and 36 pulses per complete turn). Experiment duration and time intervals of measurement can be set. An external multicounter LE3806 is necessary for data storage; it counts the number of partial and complete left and right turns depending of the adjustments made on the rotation sensors.

Rotameter

The computer interface SeDaCom allows easy exportation of data (through RS-232 serial port) in a format compatible with Excel™.

Specifications

Key Features

➤ Rotation sensor with adjustable TTL output signal

➤ Configuring experiment duration and time intervals of counting

➤ Counting the number of partial and complete left and right turns ➤ Adjustable harness with velcro ➤ Computer interface included

Parameters Measured

➤ Number of partial and complete left and right turns

Fraction of Turn

4 to 36 fraction of a circumference (selectable)

Dimensions of the Containers

400 mm diameter

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000, XP & Vista 32)

Order # Model

Product

BH2 76-0241 LE902

Rotational System Including Rotation Sensor, Rat or Mouse Harness, Bowl or Cylinder Container

BH2 76-0242 LE902-CC

Double Counter (Left & Right Turns)

BH2 76-0243 LE3806

Programmable MultiCounter with 30 Inputs (up to 15 Rota-Meter) and SedaCom Software

OPTIONS BH2 76-0244 LE902-SR

Components Included

Left & Right Rotation Sensor, Adjustable Turn Resolution

BH2 76-0245 LE902-AS

Rat Harness with Velcro and Connecting Wire

➤ Animal harness

BH2 76-0246 LE902-MT

Mouse Harness with Velcro and Connecting Wire

➤ SeDaCom software

BH2 76-0247 LE902-RP

Cylindrical or Oval Container with Supporting Rod

➤ Rotation sensor and support ➤ Container (either a bowl or a cylinder) ➤ Cables and connectors ➤ Instruction manual ➤ 2 year warranty

Options

➤ Double counter (left & right turn)

➤ Programmable counter with 30 inputs (up to 15 Rota Meter) and SeDaCom software

Rotameter Rotational behavior has proved a popular technique for screening the behavioral effects of a wide variety of lesions, drugs, and other experimental manipulations on the brain of rodents. This test is widely carried out in experiments using animal models of Parkinson’s Disease with unilateral lesions in the dopaminergic nigrostriatal system.

Citations Belzunegui S et al. (2008) Striatal carotid body graft promotes differentiation of neural progenitor cells into neurons in the olfactory bulb of adult hemiparkisonian rats. Brain Res. 1217:213-220. Martin A et al. (2008) open-field, elevated plus maze, Y-maze, and Morris water maze. Neuropsychopharmacol. 33:1667-1679 (rat, Spain) Aymerich MS et al. (2006) Consequences of unilateral nigrostriatal denervation on the thalamostriatal pathway in rats. Eur. J. Neurosci. 23(8): 2099. (rat, Spain) Bove J et al. (2006) Reversion of levodopa-induced motor fluctuations by the A2A antagonist CSC is associated with an increase in striatal preprodynorphin mRNA expression in 6-OHDA-lesioned rats. Synapse. 59(7): 435-444. (rat, Spain) Toledo-Aral JJ et al. (2003) Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body-grafted parkinsonian rats. J. Neurosci. 23(1): 141-148. (rat, Spain) Segura-Aguilar J et al. (2002) Inhibition of DT-diaphorase is a requirement for Mn3+ to produce a 6-OH-dopamine like Rotational Behavior. Neurotoxicity Research, Volume 4, Number 2, 127 – 131 (rat, Chile) Diaz-Veliz G et al. (2002) Behavioral effects of aminochrome and dopachrome injected in the rat substantia nigra. Pharmacol Biochem Behav. 73(4):843-50 (rat, Chile)

The subject wears an adjustable harness with velcro connected to the rotation sensor by a flexible tie. Wide ranges of harnesses are available to fit different animal sizes. The subject is then placed into a transparent container (cylindrical or oval) with a lateral support for a vertical stand. Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

29


Sensory & Motor HSE-HA Rodent Shocker

Now NEW versions with low current and 0.1mA accuracy available! BH2 73-0105 Rodent Shocker Sine-Wave Shock Generator with BH2 73-0108 Eye Shock Electrode for Mice and Rats

Key Features

➤ For testing anticonvulsant drugs

Specifications Stimulation Frequency

50 Hz or 60 Hz according to supply frequency

Stimulus Duration

0.1 sec to 9.9 sec in steps of 0.1 sec, selected after pressing a button, the selected time is indicated

Stimulus Energy

Up to 75 W

Output

Constant current, fully floating

Output Current Standard Version

0 to 300 mA, 0 to 150 mA, 0 to 100 mA depending on maximum stimulation voltage selected, the setting is made on a 10-turn potentiometer and the selected value is shown on the digital display

Output Current LC Version

0 to 30mA and 0 to 20mA depending on selected voltage

Limitation of Maximum Stimulation Voltage

250 V, 500 V, 750 V in 3 steps, selected by button

Digital Display

The selected stimulation current is indicated continuously in mA, the actual current applied is shown during application and can be called up later by pushing a button, the selected stimulation time is shown on pressing the TIME button, bargraph indicates the course of the stimulation time.

Supply

110 V, 60 Hz or 220 V, 50 Hz

Dimensions, H x W x D

150 x 260 x 360 mm (5.91 x 10.2 x 14.2 in)

Weight

5 kg (11 lb)

➤ For mice and rats

Order # Product

➤ Foot switch operation

BH2 73-0105 Rodent Shocker Sine-Wave Shock Generator with Foot Switch, 115 VAC, 60 Hz

Rodent Shocker

BH2 73-0106 Rodent Shocker Sine-Wave Shock Generator with Foot Switch, 230 VAC, 50 Hz

➤ Two types of electrodes are available: for eyes or ears

Cerebral seizures, preferably in mice, are produced using constant sinusoidal alternating current to determine the effect of anticonvulsant drugs. For the reliable induction of seizures it is necessary to achieve satisfactory current flow. Eye electrodes and (especially in mice) ear electrodes are used for this purpose.

BH2 73-3946 Rodent Shocker RS Type 221/LC Low Current Version, 230 VAC, 50 Hz including foot switch, output power 75 VA, maximum current at 750V is 20 mA, at 500V and 250V 30mA, selectable in steps of 0.1 mA BH2 73-3047 Rodent Shocker RS Type 221/LC Low Current Version, 115 VAC, 50 Hz including foot switch, output power 75 VA, maximum current at 750V is 20 mA, at 500V and 250V 30mA, selectable in steps of 0.1 mA BH2 73-0107 Ear Shock Electrodes for Mice and Rats, Pair BH2 73-0108 Eye Shock Electrode for Mice and Rats

30

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Analgesia Guide

Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm. For scientific and clinical purposes, pain is defined by the International Association for the Study of Pain (IASP) as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Pain is part of the body’s defense system, triggering a reflex reaction to retract from a painful stimulus, and helps adjust behavior to increase avoidance of that particular harmful situation in the future. Given its significance, physical pain is also linked to various cultural, religious, philosophical, or social issues.

The word “pain” does not equate with nociception, which is a preconscious neural activity that is normally necessary, but not sufficient, for pain. The term nociception was coined by Charles Scott Sherrington to make clear the difference between the physiological nature of nervous activity signaling tissue damage and the psychological response of pain to this physiological event. In animal models, we have to speak of “nociceptive transmission” instead of “pain transmission” since pain per se cannot be communicated. Nociception is the afferent activity produced in the peripheral and central nervous system by stimuli that have the potential to damage tissue. This activity is initiated by nociceptors that can detect mechanical, thermal or chemical changes, above a certain threshold. All nociceptors are free nerve endings of fastconducting myelinated A delta fibers or slow conducting unmyelinated C fibers, respectively responsible for fast, localized, sharp pain and slow, poorly localized, dull pain. Once stimulated, the nociceptors transmit signals that travel along the spinal cord and within the brain. Brain areas that are particularly studied in relation with pain include the somatosensory cortex which mostly accounts for the sensory discriminative dimension of pain, and the limbic system, of which the thalamus and the anterior cingulated cortex are said to be especially involved in the affective dimension. Nociception, even in the absence of pain, may trigger withdrawal reflexes and a variety of autonomic responses. The control of nociceptive transmission is complex and involves numerous peripheral and central mechanisms.

In this pathological manifestation, pain is a major symptom in many medical conditions, significantly interfering with a person’s quality of life and general functioning. Diagnosis is based on characterizing pain in various ways, according to duration, intensity, type (dull, burning or stabbing), source, or location in body. Among the most frequent technical terms for referring to abnormal perturbations in pain experiences, there are: allodynia (pain due to a stimulus which does not normally provoke pain) hyperalgesia (an increase response to a stimulus which is normally painful) and hypoalgesia (diminished pain in response to a normally painful stimulus). As an example, allodynia is a clinical feature of many painful conditions, such as neuropathies, posttherapeutic neuralgia, fibromyalgia, and migraine.

Usually pain stops without treatment or responds to simple measures such as resting or taking an analgesic, and it is then called “acute” pain. However, it may become intractable and develop into a condition called chronic pain, in which pain is no longer considered a symptom but an illness by itself.

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Analgesia Guide Behavioral Test

Behavioral Test

Tail Flick Test

Hot Plate Test

The Tail Flick Test, also known as the D’Armour and Smith Test, is a nociceptive assay based on the measured latency to avoid thermal stimulus in rodents. A thermal stimulus is applied on the tail; when the animal feels discomfort, it retracts by a sudden tail’s movement or flick. The tail flick time is then measured and used as an index of animal pain sensitivity.

The Hot-Plate Test evaluates thermal pain reflexes due to footpad contact with a heated surface. During the experiments, the animal is in a removable clear acrylic cylinder where the latency time to the first hind paw and/or jumping responses are measured.

Reasons for Choosing This Test

➤ Thermal pain sensitivity (analgesia and hyperalgesia) ➤ Evaluates responses with both spinal (licking) or surpraspinal components (jumping) ➤ Widely used in literature ➤ No need for a restrainer ➤ Sensitive for both mice rats

➤ Thermal pain sensitivity (analgesia and hyperalgesia) ➤ Objective measurement: automated detection of animal reaction time ➤ Widely used in literature ➤ Sensitive for both mice and rats ➤ Allows multiple measurements in the same animal

Reasons for Not Choosing This Test ➤ Mainly spinal response ➤ Animal habituation critical for obtaining reliable data ➤ Restrainer recommended for inexperienced users

Reasons for Choosing This Test

Reasons for Not Choosing This Test ➤ Subjective movement; visual detection of animal reaction time ➤ Allows only one evaluation per animal when jumping is measured

Related Human Disease/Applications Related Human Disease/Applications ➤ Analgesic Drug Screening ➤ Basal Pain Sensitivity Phenotyping

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➤ Analgesic Drug Screening ➤ Basal Pain Sensitivity Phenotyping

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Analgesia Guide Behavioral Test

Behavioral Test

Randall-Selitto Test

Von Frey Test

The Randall-Selitto Test involves the application of a uniformly increasing pressure on the paw to assess the threshold response to pain. The intensity of pressure causing an escape reaction was defined as the withdrawal threshold.

This test is used to assess the threshold for touch evoked sensations. Von Frey Test consists in sequentially applying filaments of different diameters until the hair that creates the noxious sensation (reflecting by a paw withdrawal effect) is found.

Reasons for Choosing This Test

Reasons for Choosing This Test

➤ Mechanical pain sensitivity (analgesia and hyperalgesia) ➤ Left and right paw discrimination ➤ Allows multiple measurements on the same animal

➤ Mechanical sensitivity to non-painful stimulus (allodynia) ➤ Left and right paw discrimination ➤ Allows multiple measurements in the same animal ➤ Sensitivity for both mice and rats

Reasons for Not Choosing This Test ➤ Mainly spinal response ➤ Animal habituation is critical for obtaining reliable data ➤ Subjective measurement: visual detection of animal reaction time ➤ Widely used in rat (paw application), needs more expertise for mice (tail or paw application)

Reasons for Not Choosing This Test ➤ Mainly spinal response ➤ Animal habituation in critical for obtaining reliable data ➤ Subjective measurements; visual detection of animal reaction test

Related Human Disease/Applications Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤

Drug Screening Phenotyping Neuropathy Inflammation Post-Operative Pain

➤ ➤ ➤ ➤ ➤

Phenotyping Neuropathy Inflammation Post-operative pain Phantom pain

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Analgesia Guide Behavioral Test

Behavioral Test

Incapacitance Test

Plethysmometer Test

In the Incapacitance Test, the animal is in a holder specially designed so the animal is comfortably positioned on two separate sensor plates. The Incapacitance device enables the quantification of spontaneous postural changes reflecting spontaneous pain. The test independently measures the weight an animal applies to each hind paw with two separate sensors. Normal rodents distribute weight equally on both paws, change of this equilibrium can reflect the level of discomfort due to an injury.

This test is typically used to follow the evolution of the inflammatory processes. This test allows evaluating paw volume, which is typically increased during inflammation. Therefore, this test is used to screen antiinflammatory potential or anti-edema properties of pharmacological substances.

Reasons for Choosing This Test ➤ Rodent paw volume evaluation ➤ Left and right paw discrimination ➤ Sensitive for both mice and rats

Reasons for Choosing This Test ➤ Spontaneous pain ➤ Left and right paw discrimination ➤ Allows multiple measurements on the same animal

Reasons for Not Choosing This Test ➤ Animal habituation is critical for obtaining reliable data ➤ Animals need to be restrained ➤ Positioning of mice for testing is difficult

Related Human Disease/Applications ➤ Neuropathy ➤ Inflammation ➤ Post-Operative Pain

Related Human Disease/Applications ➤ ➤ ➤ ➤

Anti-Inflammatory Drug Screening Anti-Edema Drug Screening Inflammation Post-Operative Plan

Behavioral Test

Thermal Place Preference Test The thermal place preference paradigm allows working on unrestrained animals that are able to choose between two compartments with different temperatures. This test is userindependent since there is no handling during the experiment. This point alone makes this test more attractive compared to traditional hot/cold plate tests. Time spent in the two compartments, crossing time and the temperature in each zone are provided in an automated manner, allowing reliable determination of the animal’s thermal pain threshold.

Reasons for Choosing This Test ➤ New test for thermal pain sensitivity ➤ Operator independent testing as animals are freely moving

Related Human Disease/Applications ➤ Drug Screening ➤ Phenotyping

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Analgesia

Tail Flick Meter for Evaluating Thermal Analgesia Tail Flick Meter

This test has proved particularly sensitive for studying the analgesic properties of pharmacological substances. It can also be used to evaluate basal thermal pain sensitivity or to study putative genetic differences among control animals. The LE7106 Tail-flick Meter consists of a stimulation unit (containing the halogen lamp for the heat stimulus) and an electronic control unit. The system can be used for rats and mice of different sizes. The animal is placed in a restrainer with its tail protruding on the platform of the stimulus unit. The animal’s tail is positioned on a slot of adjustable width equipped with a groove that guarantees a correct placement. A remote foot-switch controls the test start/stop allowing rapid handsfree experiments.

Key Features

➤ Optimal detection due to perfect alignment of heat stimulus and photo beam trigger ➤ Photo beams with adjustable sensitivity

➤ A light beam shows the point on which the heat source will focus ➤ Manual and remote timer and trigger ➤ Groove for correct tail placement ➤ Automatic cut-off

A photo beam with adjustable sensitivity detects the tail flick and the latency is automatically presented on a digital display on the control unit. Measurements of reaction time are given with a 0.1 precision. A cut-off time can be set to avoid tissue damage (by default: 20 s). The groove system for the tail and the adjustment of response sensitivity ensure optimum repeatability and reliability of results. SeDacom software supplied with the unit can be used to automatically record the results on a PC through a RS-232 port.

Specifications Control Unit Dimensions

350 (W) x 350 (D) x 130 (H)

Stimulation Unit Dimensions

400 (W) x 140 (D) x 155 (H)

Power Supply

110 V/220 V, 50/60Hz

Components Included

Material Composition

Methacrylate, halogen lamp

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000, XP and Vista 32)

➤ Stimulation unit

Maximum Number of Stations

1 per computer (multiple set-ups also available under request)

➤ Holder for rat or mouse - must specify at time of order

Certifications

CE compliant

➤ SeDaCom software

Order # Model

Product

➤ Calibration certificate

BH2 76-0293 LE7106

Tail Flick Analgesia Meter Including Restrainer, Footswitch and SeDaCom Software

➤ Computer interface, SeDaCom

Parameters Measured

➤ Time latency response to thermal stimulus ➤ Control Unit with RS-232 port to PC ➤ Mouse tail adapter ➤ Footswitch

➤ Instruction manual

➤ Cables and connectors

OPTIONS

➤ 2 year warranty

BH2 76-0114 LE7000

Thermal Printer

BH2 76-0294 LE7106T

Tail-Temperature Recorder

➤ Set of spare fuses

Options

➤ LE7000 Thermal printer

➤ LE7106T Tail-Temperature recorder

Tail Flick Meter This system features radiant heat applied on the animal’s tail; when the animal feels discomfort, it reacts by a sudden tail’s movement (tail flick) which automatically stops the stimulation and the timer for the measurement of the animal reaction time (period from the beginning of the stimulation until detection of the animal’s response).

Citations Gulati et al. (2009) Determination of Adrenergic and Imidazoline Receptor Involvement in Augmentation of Morphine and Oxycodone Analgesia by Clonidine and BMS182874. Pharmacology. 83:45-58. (rat, USA) Puente B et al. (2009) Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain. (Mouse, Spain). In press Park I et al (2008) Buprederm™, a New Transdermal Delivery System of Buprenorphine: Pharmacokinetic, Efficacy and Skin Irritancy Studies. Pharm. Res. 25(5):1052-1062 (mouse, Korea) Shamsi Meymandi M et al (2007) Intraventricular gabapentin is antinociceptive and enhances systemic morphine antinociception in rat tail flick test. DARU. 15(4):212-217 (rat, Iran) Parker AG et al. (2007) Antinociceptive effects of the aqueous extract of Brugmansia suaveolens flowers in mice. Biol. Res. For Nursing. 8(3): 234-239. (Mouse, Brazil)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Analgesia Tail Flick Meter BH2 52-9487 Tail Flick Analgesia Meter

Specifications Lamp Intensity

150 W, adjustable between 0 and 100% in 1% increments

Timer Range

0 to 99 min 59.9 secs in 0.1 sec steps

Printer Interface

Centronix parallel

Lamp Heat Control

Digital DC regulated

Dimensions, H x W x D

260 x 450 x 260 mm (10 x 18 x 10 in)

Weight

9 kg (19.8 lbs)

Order # Product BH2 52-9487 Tail Flick Analgesia Meter, 115 VAC, 60 Hz BH2 52-9495 Tail Flick Analgesia Meter, 240 VAC, 50 Hz

Key Features

➤ For rapid screening of analgesic drugs using rats (as described by D’Amour and Smith)

Tail Flick Analgesia Meter This meter measures a rat’s reaction time to radiant energy, from a 150 watt light source. The beam is focused on its tail using a parabolic reflector. The energy of the light source can be adjusted and the display indicates, as a percentage, how much energy is being utilized. An optical sensor is located underneath the focused light source. The rat should be positioned such that its tail obscures the focused light source from the sensor. When the system is started, either using the supplied footswitch or front panel mounted start key the light source illuminates and a timer starts counting in tenths of a second. When the rat’s tail flicks, indicating its pain threshold, it uncovers the sensor. This tail movement turns off the timer and light source. Reaction time can be read directly from the display in seconds and tenths of a second. A standard parallel port permits connection to a printer to record the trial number, energy level and reaction time. A calibration facility allows the light source to be set to the desired level before commencing with the experiment. Mouse version is also available, please contact Harvard Apparatus Technical Support for details.

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Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Analgesia

Hot Plate Analgesia Meter BH2 52-8570 Hot Plate Analgesia Meter with Footswitch

Specifications Temperature Range

35° to 65°C

Temperature Stability

±0.3°C

Temperature Control

Digital proportional PWM

Timer

Digital readout in 0.1 sec increments

Timer Range

0 to 9 mins 59 secs 9 tenths of a sec

Remote

Momentary make to start/stop

Remote Socket

6.35 mm 2 pole jack

Animal Container

Two furnished, large round cylinders

Mains Supply Voltage

115 VAC/230 VAC, 50/60 Hz (factory set)

Dimensions, H x W x D

128 x 275 x 293 mm (5 x 10.8 x 11.5 in)

Weight

4.5 kg (9.9 lb)

Order # Product BH2 52-8570 Hot Plate Analgesia Meter 110 to 115 VAC, 60 Hz

Key Features

BH2 52-8588 Hot Plate Analgesia Meter 220 to 230 VAC, 50 Hz

➤ Digital display of plate temperature ➤ Digital timer with remote start stop

➤ Accurate temperature control from 35°C to 65°C (±0.3°C)

Hot Plate Analgesia Meter

The Harvard Apparatus UK Hot Plate Analgesia Meter is a sophisticated temperature control and timing system, and has been designed to perform rapid and precise screening of the narcotic type analgesic drugs (Morphine, Codeine, etc.) according to the Eddy and Leimback hot plate test. This method evaluates the reaction time of mice when a heat stimulus is applied to the plantar surface. This reaction time increases when a central analgesic is administered to the animal. This system can be used with both mice and rats. Utilizing a simple user interface the user can quickly and easily set up the required hot plate temperature and a large easy to read LED display shows the current temperature. The timer requires a single press of the Start / Stop Key to start and another press to stop, with reset automatically executed when timing is initiated. This function is also duplicated by a remote Start/Stop footswitch (supplied). The reaction time is again clearly displayed on a large LED display. Using digital electronics, the hot plate temperature is constantly monitored and regulated to ensure the actual temperature and the desired temperature accurately match. The system also monitors the heating characteristics of the system and uses this data to minimize heating overshoot, providing faster temperature stabilization.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

37


Analgesia

Hot-Plate for Evaluating Thermal Analgesia Hot Plate

Hot Plate

The LE7406 Hot-Plate performs rapid and precise screening of analgesic drug properties on small-laboratory animals according to the ‘hot-plate test’. The animal’s pain sensitivity alterations induced by a specific experimental context change and/or genetic manipulations can also be evaluated through this method. The hot-plate test, initially described by N.B. Eddy and D. Leimbach (1953), evaluates thermal pain reflexes due to footpad contact with a heated surface. During the experiments, the animal is confined in a removable clear acrylic cylinder where the latency time to the first hind paw or/and jumping responses are measured. In the LE7406 Hot-Plate, a thick aluminum plate (10 mm) provides a high temperature stability and even surface distribution. The plate temperature can be held at a set point between 45 and 62°C (± 0.1°C) by multiple proportional feedback circuits that minimize overshoot. A builtin timer activated by an external foot switch allows precise measurement of reaction time (0.1 sec precision). A remote foot-switch controls the test start/stop allowing rapid hands-free experiments. The operator can read the animal reaction time from the display or from a PC computer using the SeDaCom software. Trial number, plate temperature and reaction time are then sent to the PC through a RS-232 port.

Specifications Base Dimensions

200 (W) x 300 (D) x 110 (H) mm

Plate Dimensions

200 (D) mm

Cylinder Dimensions

200 (D) x 250 (H) mm

Operating Temperature

45 to 62 degrees Celsius; 0.1 steps

Key Features

Reaction Time

3 digits, 0.01 sec increment

Material Composition

Clear methacrylate (animal holder), aluminum (plate)

➤ Built-in electronic timer

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000 and Vista)

Maximum Number of Stations

1 per computer (multiple set-ups also available under request)

Power Requirements

110V or 220V, 50/60Hz

Certifications

CE compliant

➤ Digital set point

➤ Foot switch timing operation ➤ Computer interface

Parameters Measured

➤ Time latency to 'paw licking' ➤ Time latency to 'jumping'

Components Included ➤ Base with heating plate ➤ Footswitch

➤ Data transfer software included (SeDaCom) ➤ Cables and connectors

➤ Certificate of calibration ➤ Instruction manual ➤ Set of spare fuses ➤ 2 year warranty

Options

➤ LE7000 Thermal printer

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Order # Model

Product

BH2 76-0113 LE 7406

Hot-Plate Thermal Analgesia Meter Including SeDaCom Software

OPTIONS BH2 76-0114 LE7000

Thermal Printer

Citations Puentes B et al. (2009) Sigma-1 receptors regulate activity-induced spinal sensitization and neuropathic pain after peripheral nerve injury. Pain. 145(3):294-303. (mouse, Spain) Viosca J et al. (2009) Germline expression of H-RasG12V causes neurological deficits associated to Costello syndrome. Genes, Brain Behav. 8(1):60-71. (mouse, Spain) Luvisetto S et al. (2008) Enhancement of anxiety, facilitation of avoidance behavior, and occurrence of adultonset obesity in mice lacking mitochondrial cyclophilin D. Neuroscience. 155(3):585-596 (mouse, USA) Sudo RT et al. (2008) The Antinociceptive Activity of a New alpha-2 Adrenoceptor Agonist (PT-31) in Mice. Anesthesiology 2007; 107: A1455. (Mouse, Brazil) Camarasa J et al. (2006) Association of caffeine to MDMA does not increase antinociception by potentiates adverse effects of this recreational drug. Brain Res. 1111:72-82. (mice, Spain) Grillet N et al. (2005) Generation and characterization of Rgs4 mutant mice. Mol. Cell. Biol. 25(10): 4221-4228. (mice, France)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Analgesia

Hot/Cold Plate for Testing Animal Sensitivity Hot/Cold Plate Anagelsia Meter

Hot/Cold Plate Panlab/Harvard Apparatus Hot/Cold Plate Analgesia Meter is based on a metal plate which can be heated to 65°C and cooled to -3°C (with an ambient temperature between 20°C and 25°C). An electronic thermostat maintains the plate's temperature and a front panel digital thermometer displays the current plate temperature. The animal’s pain sensitivity resulting from exposure to heat or cold is tested by placing the animal on the surface of the plate and starting a built-in timer. The operator stops the timer at the instant the animal lifts its paw from the plate, reacting to the discomfort. The front panel timer then displays the number of seconds the animal took to react. Animal reaction time is a measurement of animal resistance to pain and is used to measure efficacy of analgesics. The plate is designed to be very simple to use and very fast to reach the set temperature (as example from ambient to 4°C, the most used threshold value, it takes less than 10 minutes, and from 4°C to 65°C it takes only 5 minutes). The Hot/Cold Plate, is accurate to less than 0.5°C (EEC metrology standard) and perfectly constant in the animal holder system. The preset temperature will not change for more than 0.1°C when a 400g rat is placed on the plate, and return to the set temperature is almost immediate. In addition, the instrument can be adjusted to be used for “TEMPERATURE RAMPS”. Predefined by the user, this feature is mainly used for studies with telemetry implants. In addition to displaying the reaction time, the Cold/Hot Plate Analgesia Meter is capable of sending the same via USB interface to a computer. The operator can start and stop the timer with the front panel start/stop switch or with the included footswitch, which allows “hands-free” operation.

Key Features

➤ Unmatched temperature stability and control for both hot and cold ➤ Fast acclimation to set temperatures

➤ Homogeneous temperature surface distribution

➤ BSRamp software will allow the user to define temperature ramps (slope in °C/min, start and end points) and store results

Parameters Measured

➤ Animal reaction time to hot or cold stimulus

Components Included ➤ Stimulation Unit LE7420 ➤ Footswitch ➤ USB cable

➤ BSRamp software

➤ Instruction manual ➤ One year warranty

Specifications Temperature Range

-3°C to 65°C (in 20°C to 25°C ambient environment, 50% RH)

Temperature Accuracy

±0.5°C

Temperature Uniformity

±0.5°C on Plate

Power Requirements

110 V/220 V automatic, 100W

Dimensions: Plate

165 x 165 mm

Control Unit

305 x 280 x 158 mm

Weight

6.5 kg

Order # Model

Product

BH2 76-0112 LE7420

Hot/Cold Plate Including BSRamp Software

Citations Noel J et al. (2009) The mechano-activated K+ channels TRAAK and TREK-1 control both warm and cold perception. EMBO J. 28(9):1308-1318. (mouse, France) Yalcin I et al. (2009) Differentiating Thermal Allodynia and Hyperalgesia Using Dynamic Hot and Cold Plate in Rodents. The Journal of pain. 10(7):767-773. (mouse, rat, France)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Analgesia

NEW Thermal Place Preference Thermal Place Preference

Thermal Place Preference This behavioral assay will allow monitoring of temperature preferences, nociceptive thresholds and investigate the role of a given gene or compound on these thresholds. As advised by A. Moqrich and published in Moqrich et al (Science 2005, 307: 1468-72), this test allows researchers to work on unrestrained animals whom are free to choose their preferred position between two compartments at different temperatures. Completely investigator-independent, the Two Temperature Choice Test provides a response without any action from the user and the obtained value is a threshold temperature of range of temperatures. Using automatic detection software (optional), the user sets the temperature of each zone, defines a protocol of temperature changes or ramps, and starts the measurement process. Two animals can be observed simultaneously and independently, making the system remarkable efficient. The animals are video tracked and the software records their position vs. temperature and time. When the optional automatic detection software is not used, temperatures must be defined manually and the user must measure the time and animal position.

Specifications

Key Features

➤ Easily monitor thermal place preference and nociceptive thresholds ➤ Unrestrained animals allows for maximum accuracy

➤ Optional Automatic Detection Software eliminates the user subjectivity by establishing an automatic response

Parameters Measured

➤ Time spent in each zone ➤ Time of zone trespassing

➤ Temperature of each zone

Temperature Range

-3°C to +65°C (room temperature 20 to 25°C)

Temperature Accuracy

± 0.3°C

Power Supply

150 Watts, 120/240 VAC

Dimensions (L x W x H)

32 x 57 x 45.5 cm (12.6 x 22.4 x 17.9 in) including cage

Weight

14 kg (30.9 lbs)

Animal Cage

330 x 165 x 300 mm (13 x 6.5 x 11.8 in)

Animal Cage Material

Clear plexiglass

Computer Requirements

Windows® XP/Vista/Seven (coming soon) PC with 1 GO ram and 3 USB ports

Order # Model

Product

BH2 76-0475 T2CT

Thermal Place Preference

BH2 76-0476 T2CTSW

Thermal Place Preference Software

Options

➤ Automatic detection software – which includes tripod, 3 USB cables and USB Camera

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Analgesia

NEW Thermal Gradient Test Thermal Gradient Test

Independent Thermal Test Demonstrates Place Preference and Temperature Comfort Thresholds for Rodents! As described by Moqrich et al. 2005, our Thermal Gradient Test monitors thermal nociception completely independently on freely moving rodents. A continuous temperature gradient (15 to 55°C) is established over a 125 cm long base plate on which the animal is free to walk. After an exploration period of acclimation, the animal clearly shows a distinct zone preference. Our model is an automated system with maintains the temperature gradient stable over the surface and over time. Two models are available testing either 2 mice/1 rat or 4 mice/2 rats. The accompanying software, coupled to a video camera, displays for each animal the time spent in each temperature zone, together with overall distance travelled. The encrypted data and video images are recorded synchronously in real time during the experiments and the user is able to replay the files to analyze or review.

Specifications Overall Dimensions (L x W x H): 2 mice/1 rat

139 x 30 x 40 cm (54.7 x 11.8 x 15.6 in)

4 mice/2 rat

139 x 43 x 25 cm (54.7 x 16.9 x 9.8 in)

Overall Weight:

Key Features

➤ Continuous thermal gradient established over a 125 cm long base plate ➤ Monitor independently and simultaneously 2 mice/1 rat or 4 mice/2 rats with our two different models!

Parameters Measured

➤ Up to 20 temperature zones measured per animal ➤ Time spent in each temperatures zone ➤ Temperature of zone over time period ➤ Overall distance travelled

Components Included ➤ Two thermal units ➤ Controllers ➤ Cage

2 mice/1 rat

25 kg (33.1 lbs)

4 mice/2 rat

45 kg (44.1 lbs)

Power Supply

110/220 Volts

Number of Lanes

2 mice/1 rat Mouse 4 mice/2 rat Rat

Lane Dimensions: 2 mice/1 rat

125 x 10 x 15 cm (49.2 x 3.9 x 5.9 in)

4 mice/2 rat

125 x 10 x 12 cm (49.2 x 3.9 x 4.7 in)

Temperature Range

15 to 55° C at plate surface 20 to 25°, 50% RH at environment

Temperature Stability

1°C surface, over time

System Material: Base Plate

Aluminum Alloy

Walls

Gray PPC

Top Cover

Transparent PPC

Computer Requirements

➤ Base plate

PC 2Go Ram, Windows® XP/Vista/Seven (coming soon) with 3 USB ports, webcam and mini-USB cables included with system

Order # Model

Product

BH2 76-0477 TGT2

Thermal Gradient Test, 2 Mice / 1 Rat

BH2 76-0478 TGT4

Thermal Gradient Test, 4 Mice / 2 Rat

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Analgesia

NEW Electronic Von Frey for Evaluating Mechanical Allodynia NEW & Unique - Electronic Von Frey! •

Internal statistical computations allows direct reading of average value, standard deviation and variability in subject groups and up to 100 animals

The electronic model of Von Frey filament combines ease of use and rapidity for the determination of the mechanical sensitivity threshold in rodents. The Von Frey filament is applied against the central edge of the animal hind paw. Paw withdrawal caused by the stimulation is registered as a response. The corresponding force applied is recorded by the system and displayed on the large backlighted screen of the Von Frey unit with a resolution of 0.1 grams. Different from the procedure using classical Von Frey filaments, the threshold value can be obtained in only one test, and in a highly reproducible manner. A foot switch is provided to reset the screen and carry out rapid hands-free experiments. RSIC software can be used to automatically record the results on a PC through a RS-232 port. The electronic Von Frey can be supplied with a National Standard Linked calibration certificate (ISO 9000), and an EMC conformity agreement.

Specifications Measurement Range

0 to 500 g (5N), 120% overload allowed without causing any damage to the sensor

Precision: 0.1 g

Accuracy

0.2 g

Temperature Compensation

from 0 to 50°C

Statistical Functions

Average value and standard deviation are computed for all the data stored

Internal Memory

up to 100 values

Power Supply

110-220 V (other voltages on request)

➤ Elimination of the problems of filament standardization

Weight

6.5 kg

➤ The end-point value is automatically recorded

Order # Model

Product

BH2 76-0487 BSBIOEVF3

Electronic Von Frey Complete with Accessories & Suitcase 110 or 220 VAC

➤ Peak force eliciting an animal response

BH2 76-0488 BSBIOEVFD

Hard plastic tips, 10 units

BH2 76-0489 BSBIOEVFRS

Elastic (spring) tips, 1 unit

➤ Electronic Von Frey unit

BH2 76-0484 BSBIORSIC

Data Acquisition RSIC Software Windows® XP (dongle & CD)

Key Features

➤ Provides objective and accurate data

➤ The threshold value can be obtained in only one test, and in a highly reproducible manner ➤ Stimulation of areas of equal size

Parameters Measured

➤ Current force applied on the animal paw (grams)

Components Included

➤ 10 disposable plastic tips

➤ 1 spring tip for thresholds between 0 and 10 grams ➤ Footswitch to reset the display to zero ➤ Carrying case for transport

Options

➤ RSIC software

➤ National Standard Linked Calibration Certificate ➤ EMC conformity agreement

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Resolution

Citations Casals-Diaz L et al. (2009) Nociceptive responses and spinal plastic changes of afferent C-fibers in three neuropathic pain models induced by sciatic nerve injury in the rat. Exp. Neurol. 217(1):84-95. (rat, Spain) Duale C et al. (2008) Cutaneous Amitriptyline in Human Volunteers: Differential Effects on the Components of Sensory Information. Anesthesiology. 108(4):714-721 (Human, France) Laalou FZ et al (2008) Involvement of the Basal Cholinergic Forebrain in the Mediation of General (Propofol) AnesthesiaAnesthesiology. 108(5):888-896 (Rat, France) Lefaucheur JP et al (2008) Motor cortex rTMS in chronic neuropathic pain: pain relief is associated with thermal sensory perception improvement. J Neurol Neurosurg Psychiatry. 79(9):1044-9 (Human, France) Thibault K et al. (2008) Antinociceptive and anti-allodynic effects of oral PL37, a complete inhibitor of enkephalin-catabolizing enzymes, in a rat model of peripheral neuropathic pain induced by vincristine. Eur. J. Pharmacol. 600(1-3):71-77. (rat, France) Vivo M et al (2008) Immediate electrical stimulation enhances regeneration and reinnervation and modulates spinal plastic changes after sciatic nerve injury and repair. Exp. Neurol. 211(1):180-193 (Rat, Spain)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Analgesia

Heat-Flux Infrared Radiometer Heat-Flux Infrared Radiometer The Heat-Flux Infrared Radiometer has been designed to calibrate I.R. sources, in particular the classic Plantar Test, to make sure they deliver the same power flux and hence a nociceptive stimulus of the same intensity. This Heat-Flux Infrared Radiometer is a battery operated, self sufficient instrument complete with infrared probe, digital meter and adaptors for the Plantar Test. The Infrared Radiometer enables the experimenter to: i) Check (and adjust if necessary) the infrared emission. In fact, the infrared output of the Plantar Test may in the course of one to two years undergo to 2-3% reduction, due to dust gathered on the optics, blackening of the infrared bulb, accidental knocks, aging of components due to thermal cycles, etc. Moreover, in case the bulb is replaced or the electronics serviced, output alteration of more significant magnitude, say, 8-10%, may take place. ii) Make sure that two or more Plantar-Test units deliver thermal nociceptive stimuli of exactly the same intensity. Balance them, if necessary. iii) Know the infrared energy (1 mW for the duration of 1sec corresponds to 1 mJ) in absolute terms, a useful information to compare with any equal or different method/instrument described in the literature.

Key Features

➤ Takes only seconds to use ➤ Digital Display

➤ Calibrates the infrared emission of Plantar Test to ensure uniform power flux delivery for all trials

Parameters Measured

➤ Stimulus intensity in mW/cm2

The measuring only requires a few seconds. The I.R. probe is positioned on the Plantar Test after the suitable adaptor is fitted on the threaded head of its heat-sink. The reading on the digital display gives the I.R. power output in mW per square centimeter. The calibration, if necessary, of the I.R. radiation source, is carried out by adjusting the supply current of the I.R. bulb, see the instruction manuals of the Plantar Test. The Heat-Flux Infrared Radiometer Complete Package includes: Digital Heat-Flux Meter (complete with cable/connector & 9V battery), Plantar Test adaptor and I.R. Probe neatly lodged in a sturdy plastic case with punched foam lining.

Specifications Dimensions, H x W x D

11 x 37 x 32 cm (4.3 x 14.6 x 12.6 in)

Weight

2.00 kg (4.4 lbs)

Shipping Weight

3.20 kg (7.1 lbs)

Order # Model

Product

BH2 72-6703 37300

Heat-Flux Infrared Radiometer, Standard Package

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43


Analgesia

Plantar Test (Hargreaves’ Method)

Key Features

➤ For measurement of hyperalgesia to thermal stimulation in unrestrained animals ➤ Automatic objective detection of latency to withdrawal ➤ Validity unaffected by repeated testing

➤ Greater bioassay sensitivity than other thermal or mechanical tests ➤ Each animal can serve as its own control

➤ Dedicated software and memory key included!

Components Included ➤ Movable infrared source

➤ Glass pane onto which the animal enclosure is located ➤ Controller

➤ Multiple configuration animal enclosure can be optimized for mice or rats of any size

Plantar Test The Plantar Test (Hargreaves’ Method) enables the researcher to discern a peripherally mediated response to thermal stimulation caused by drugs in the unrestrained rat or mouse. The animal is placed into one of the compartments. After an acclimation period, the infrared source is placed under the glass floor and is positioned by the operator directly beneath the hind paw. A trial is commenced by depressing a key which turns on the infrared source and starts a digital solid state timer.

counter. The withdrawal latency is calculated to the nearest 0.1 second. The 3-compartment enclosure has been provided to speed up the test when a number of animals are involved. In each compartment the animal is unrestrained. The Heat-Flux Infrared Radiometer 37300 has been designed to calibrate infrared sources, in particular the Plantar Test.

Calibration Radiometer

Each plantar test is accurately calibrated via an infrared radiometer to make sure that its infrared source delivers the same power flux (expressed in mW per square cm) and hence a nociceptive stimulus of the same intensity. The end user should consider the Heat-Flow Infrared Radiometer Model an extremely useful accessory. This Infrared Radiometer is a battery operated, self sufficient instrument complete with infrared probe, digital meter and adaptors for the Plantar Test. All parts are neatly lodged in a sturdy plastic case with punched foam lining. This Radiometer Enables the Experimenter to: i) Make sure that two or more Plantar-Test units deliver thermal nociceptive stimuli of exactly the same intensity. ii) Know the I.R. energy (1 mW for the duration of 1s corresponds to 1 mJ) in absolute terms, a useful datum to compare with any equal or different method/instrument described in the literature.

Data Acquisition

The Plantar Test controller stores experimental data internally and can directly export data to PC USB or serial ports. A memory key is included for easy transfer and files can be opened in Excel. Communications are managed by included data acquisition software or by optional BH2 72-6671 Win-DAS.

When the animal feels the stimulus, it will withdraw its paw. The withdrawal of the paw causes a sudden drop in the reflected radiation which switches off the infrared source and stops the reaction time

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Analgesia

Plantar Test (Hargreaves’ Method) (continued) Specifications Starting

Via keys on the I.R. vessel or controller

Infrared Intensity

Adjustable in the interval 10 to 99 (in one digit steps)

Reaction Time

Three-digit LED display, 0.1 second steps

Infrared Bulb

Halogen “Bellaphot”

Calibration

Via appropriate I.R. radiometer

Connection to PC

USB

Power Requirement

115/230 V, 50/60 Hz, 60 VA maximum

Operating Temperature

15° to 30°C

Dimensions (assembled)

85 x 40 x 35 cm (33.5 x 15.7 x 13.8 in)

Weight

13.00 kg (28.7 lb)

Shipping Weight

27.50 kg (60.6 lb) approximately

Order # Model

Product

BH2 72-6692 37370

Plantar Test, Rats and Mice

BH2 72-6703 37300

Heat-Flux Infrared Radiometer

BH2 72-6695 37370-003

Platform with Supporting Columns

BH2 72-6696 7370-005

Framed Glass Pane

ACCESSORIES

REPLACEMENT PARTS

BH2 72-6698 E-HR002

Spare Bulb

BH2 72-7957 37000-006

Multiple Configuration Animal Enclosure

CITATIONS Methods Paper: M.J Field et al. (1999) Detection of Static and Dynamic Components of Mechanical Allodynia in Rat Models of Neuropathic Pain; Are they Signalled by Distinct Primary Sensory Neurosnes? Pain 83: 303-311 Lembeck, Fred (1999) Epibatine: High Potency and Broad Spectrum Activity on Neuonal and Neuromuscular Nicotinic Acetylcholine Receptors. Naunyn-Schmiedeberg’s Arch. Pharmacol. 359:378-385 Hartmut Buerkle et al. (1999) Experimental Arthritis I nteh Rat Does Not Alter the Analgesic Potency of Intrathecal or Intraarticular Morphine. Anesth. Analg. 89:403-408 K.M. Hargreaves, R. Dubner, F. Brown, C. Flores and J. Joris: “A New and Sensitive Method for Measuring Thermal Nociception in Cutaneous Hyperalgesia.” Pain 32: 77-88, 1988. Additional Papers: K.M. Hargreaves, R. Dubner and J. Joris: “Peripheral Action of Opiates in the Blockade of Carrageenan-Induced Inflammation” Pain Research and Clinical Management. Vol. 3. Elsevier Science Publishers, Amsterdam: 55-60, 1988 G. Benneth and Y.K. Xie: “A Peripheral Neuropathy in Rat that Produces Disorders of Pain Sensation Like Those Seen in Man” Pain 33: 87-107, 1988. M. Iadarola and G. Draisci: “Elevation of Spinal Cord Dynorphin mRNA Compared to Dorsal Root Ganglion Peptide mRNAs During Peripheral Inflammation” In: The Arthritic Rat as a Model of Clinical Pain? by J. Besson and G. Guilbaud (eds.) Elsevier Press, Amsterdam: 173-183, 1988. A. Costello and K.M. Hargreaves: “Suppression of Carrageenan-Induced Hyperalgesia. Edema and Hyperthermia by a Bradykinin Antagonist” European J. Pharmacol., 1989. K.M. Hargreaves, R. Dubner and A. Costello: “Corticotropin Releasing Factor (CRF) has a Peripheral Site of Action for Antinociception” European J. Pharmacol., 1989. J. Hylden, R. Nahin, R. Traub and R. Dubner: “Expansion of Receptive Fields of Spinal Lamina I Protection Neurons in Rats with Unilateral Adjuvant-Induced Inflamma-tion: The Contribution of Central Dorsal Horn Mechanisms” Pain 37: 229-244, 1989.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

45


Analgesia

Dynamic Plantar Aesthesiometer Following acclimation after cessation of exploratory behavior, the operator places the touch-stimulator unit under the animal’s paw, using the adjustable angled-mirror to position the filament below the target area of the paw. A START key is provided at both sides of the handle of the touch-stimulator vessel, to help both left- and right-handed operators, as well as the controller Pressing START invokes the following automatic sequence: a. An electro-dynamic actuator of proprietary design lifts a straight metal filament b. The filament touches the plantar surface and begins to exert an upward force below the threshold of feeling c. The force increases (at your preset rate of application), until a stop signal is attained. The stop signal is either the animal removing the paw or the point at which greatest preset force is met.

Key Features

➤ Models for mice or rats

➤ For the assessment of animal sensitivity to the light touch of the paw ➤ Computer compatibility, direct connection to a PC ➤ Graphic display

➤ Software included!

➤ Memory key for easy data acquisition

Components Included

➤ Movable touch-stimulator unit

➤ Framed metal mesh and base with columns

➤ Modular animal enclosure, offering 3 to 12 spaces ➤ Microprocessor controlled electronic unit

Dynamic Plantar Aesthesiometer The Dynamic Plantar Aesthesiometer consists of a movable forceactuator below a network platform upon which the operator deposits the rodent. A Perspex enclosure renders the animal unrestrained for the duration of the experiment. The operator places the actuator beneath the paw (proper placement ensured via an angled mirror) and the actuator confers a use-defined force on a Von Frey-type filament. The filament exerts an increasing force to the plantar surface, starting below the threshold of detection and increasing until the animal removes its paw. At the retraction reflex movement when the paw is withdrawn, the instrument registers and displays the actual force at which paw withdrawal occurred. The Dynamic Plantar Aesthesiometer is a new instrument for the assessment of “touch sensitivity” on the plantar surface of the rodents. Somesthetic (mechanical) stimulation has a long history of effective clinical use to diagnose pathologies of hyper- or hypo- analgesia, brought about by drugs, neural pathology or experimental lesions, etc., in model systems and experimental systems using laboratory animals. The electronic unit is enclosed into a cylindrical case of original design, with graphic LCD display, USB port and four membrane switches for setting experimental parameters. The unit also has an internal memory for data storage, scrolling screen review, and optional output to PC. The rat, mouse or other small rodent moves about freely in one of the compartments of the enclosure, positioned on the metal mesh surface.

46

The actuator filament (0.5 mm diameter) produces force over the entire range of all typical anesthesiometer test devices. Paw withdrawal reflex is automatically recorded using two metrics: the latency until withdrawal, in seconds, and the force at which paw was withdrawn, in grams.

Data Acquisition

The Dynamic Plantar Aesthesiometer features direct PC output. Internallystored data can be routed to the PC serial port or USB. Data output is achieved through the dedicated acquisition package or the optional WinDAS Software. This Windows® based Data Acquisition Software Package stores the data into individual files which make the date easily exportable to most statistical analysis packages available on the market. Each Aesthsiometer is supplied complete with the following components: Electronic Unit, Touch Stimulator, complete with Filament Actuator and Adjustable Angled-Mirror, Platform with Supporting Columns, Framed Metal Mesh Testing Surface, modular Animal Enclosure, Set of Two 0.5 mm Diameter Stainless-Steel Filaments and Two Calibration Weights (5 & 50 g), Mains Cord, Set of 2 fuses for either 230V or 115V operation, and Instruction Manual.

Specifications Starting

Via keys on the touch-stimulator vessel

Force Range

0 to 50.0 grams or 0-5 grams in 0.5 g steps

Force Increasing Rate

Adjustable in the interval 1 to 20 seconds, in 1 s steps

Filament Travel

12 mm

Latency Time

Read-out on the graphic display, in 0.1s steps

Connection to PC

Through USB. See DATA ACQUISITION

Power Requirements

115 V/230 V, 50/60 Hz, 20 W maximum

Dimensions: Electronic Unit

12 x 26 x 13 cm (4.73 x 10.2 x 5.1 in) (H x W x D)

Assembled Platform

40 x 50 x 32 cm (15.75 x 19.7 x 12.6 in)

Total Weight

10.20 kg (22.5 lb)

Shipping Weight

18.50 kg (40.8 lb), approximately

Order # Model

Product

BH2 72-6704 37450

Dynamic Plantar Aesthesiometer

BH2 72-6712 37400-321

Set of Two 0.5 mm Diameter Stainless-Steel Filaments and Two Calibration Weights (5 & 50 G)

ACCESSORIES

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Analgesia

Rat Paw Pressure for Evaluating Mechanical Pain The conic point is mounted on an extensiometric load cell, making possible the visualization on the digital display of the current force applied at each moment of the test (grams). The motor and tip units are mounted on a pivoting stand preventing any excess pressure on the animal paw. The control unit makes possible the adjustment of the force transducer, balance and reset, as well as the selection of the stepmotor current speed.

Rat Paw Pressure Analgesia Meter

Key Features

➤ Digital display

➤ Pressure increasing rate adjustment

➤ Data transfer software included (SeDaCom) ➤ Footswitch control

Parameters Measured

➤ Pressure applied on the paw until the withdrawal or animal vocalizes (rats) ➤ Pressure applied on the tail until withdrawn (mice)

➤ Pressure applied on the paw until a flexor response of the toes (mice)

Components Included

➤ Control unit with RS-232 communication port to PC ➤ Stimulation unit ➤ Pedal switch

➤ Flat and pointed tip points ➤ SeDaCom software ➤ Instruction manual

➤ Cables and connectors ➤ Set of spare fuses ➤ 2 year warranty

Options

➤ LE7000 thermal printer

Rat Paw Pressure Analgesia Meter The Randall & Selitto test is based on determination of the animal threshold response to pain induced in the paw by the application of a increasing pressure. In the LE7306 paw-pressure, a stimulation unit allows the gradual increase (at selectable rates) of the pressure applied on the animal paw. The pressure increase is achieved by a step-motor inducing the progressive advancement of a sliding support with a distal conic tip (1 mm diameter).

A remote foot-switch controls the motor turn on/off allowing rapid hands-free experiments. An automatic system is activated once the distal extreme of the sliding support track is reached or when the pedal is released at the test ending point. Then, the motor reverse its rotation at its higher speed, sliding up the conic tip again. SeDacom software supplied with the unit can be used to automatically record the results on a PC through a RS-232 port.

Specifications Power Supply

110 V/220 V, 50/60Hz

Stimuli Resolution

1 gram

Maximum Stimuli

999 gram

Material Composition

Methacrylate

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000, XP and Vista)

Maximum Number of Stations

1 per computer (multiple set-ups also availableunder request)

Certifications

CE Compliant

Control Unit Dimensions

350 (W) x 350 (D) x 130 (H) mm

Stimulation Unit Dimensions

150 (W) x 210 (D) x 166 (H) mm

Order # Model

Product

BH2 76-0234 LE7306

Rat Paw Pressure Analgesia-Meter Including SeDaCom Software

OPTIONS BH2 76-0114 LE7000

Thermal Printer

Citations Fernández-Dueñas V et al (2008) Adjuvant effect of caffeine on acetylsalicylic acid antinociception: Prostaglandin E2 synthesis determination in carrageenan-induced peripheral inflammation in rat Eur. J. Pain, 12(Issue 2):157-163 (Rat, Spain) Célérier E et al. (2006) Opioid-induced hyperalgesia in a murine model of postoperative pain: role of nitric oxide generated from the inducible nitric oxide synthase. Anesthesiology 104(3): 546-555. (Pawpressure, Mice, Spain) Romero A et al (2005) Anti-exudative effects of opioid receptor agonists in a rat model of carrageenaninduced acute inflammation of the paw. Eur. J. Pharmacol. 511(2-3):207-217. (Rat, Spain) Célérier E et al. (2004) Prevention of fentanyl-induced delayed pronociceptive effects in mice lacking the protein kinase C-gamma gene. Neuropharmacol. 46:264-272. (Tail-pressure, Mouse, Spain) Al-Naggar TB et al. (2003) Neuropharmacological activity of Nigella sativa L. extracts. J. Ethnopharmacol. 88(1): 63-68. (Rat, Spain) Gutierrez M et al. (2003) Interactions of acute morphine with chronic imipramine and fluvoxamine treatment on the antinociceptive effect in arthritic rats. 352(Issue 1): 37-40. (Rat, Spain) Martin M et al. (2003) Acute antinociceptive responses in single and combinatorial opioid receptor knockout mice: distinct mu, delta and kappa tones Eur. J. .Neurosci. 17(4):701 (Tail-pressure, Mouse, Spain) Martin M et al. (2003) Morphine withdrawal is modified in pituitary adenylate cyclase-activating polypeptide type I-receptor-deficient mice. Mol. Brain Res. 110(1):109-118. (Mouse, Spain)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

47


Analgesia

Plethysmometer for Evaluating Paw Volume Digital Water Plethysmometer

Digital Water Plethysmometer Key Features

➤ Computer interface

➤ “Check solution” status button

➤ Conductive solution is easy to prepare or source ➤ Data transfer software included (SeDaCom) ➤ Footswitch control

➤ Automatic zero adjustment

Parameters Measured ➤ Paw volume (ml)

Components Included

➤ Control Unit with RS-232 communication port to PC ➤ Pedal switch

➤ Stimulation unit

➤ Conductive solution (100 ml bottle) ➤ 1ml, 3ml or 5ml cell with electrode ➤ 1ml or 3ml volume gauge ➤ SeDaCom software ➤ Instruction manual

➤ Cables and connectors ➤ Set of spare fuses

➤ Certificate of calibration ➤ 2 year warranty

Options

➤ LE7000 Thermal printer

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The Digital Water Plethysmometer is designed to provide a highly useful tool in the measurement of small volume changes. This test is typically used to follow the evolution of the inflammatory response experimentally induced in rodents and to screen potential antiinflammatory or anti-oedema properties of pharmacological substances. The volume transducer is formed by two Perspex tubes interconnected and filled with a conductive solution and a platinum electrode for each chamber. All the system is supported by a stand (included) that can be placed over the control unit. The water displacement produced by the immersion of the animal paw in the measuring tube is reflected into the second tube, inducing a change in the conductance between the two platinum electrodes. The Plethysmometer Control Unit detects the conductance changes and generates an output signal to the digital display indicating the volume displacement measured (0.01 ml resolution). The current value remains in the digital display until a new trial starts. The Control Unit is automatically zeroed between successive readings, thus making intermediate adjustments unnecessary. The system includes as standard a volume transducer with its related calibrator and a 100 ml solution. A remote footswitch allows rapid hands-free experiments and can be used to set control the end point of the measurement. SeDaCom software supplied with the unit can be used to automatically record the results on a PC through a RS-232 port.


Analgesia

Plethysmometer for Evaluating Paw Volume (Continued) Specifications Control Unit Dimensions

280 (W) x 280 (D) x 110 (H)

Stimulation Unit Dimensions

230 (W) x 220 (D) x 300 (H)

Power Supply

220 V/110 V, 50/60Hz

Starting

By panel key or pedal switch

Resolution

3 digits, 0.01 steps

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000, XP and Vista)

Material Composition

Clear methacrylate (cell), stainless steel (stand), platinum (electrode)

Maximum Number of Stations

1 per computer (multiple set-ups also available under request)

Certifications

CE compliant

Order # Model

Product

BH2 76-0220 LE7500

Digital Water Plethysmometer Including 3 ml Cell and SeDaCom Software

OPTIONS BH2 76-0221 LE7504

1 ml Cell with Electrode

BH2 76-0222 LE7505

5 ml Cell with Electrode

BH2 76-0223 LE7503

3 ml Cell with Electrode

BH2 76-0224 LE7506

Platinum Electrode

BH2 76-0225 LE75301

1 ml Calibrator for Plethysmometer

BH2 76-0226 LE75303

3 ml Calibrator for Plethysmometer

BH2 76-0114 LE7000

Thermal Printer

Citations Bignotto L et al. (2009) Anti-inflammatory effect of lycopene on carrageenan-induced paw oedema and hepatic ischaemia–reperfusion in the rat. British Journal of Nutrition 102:126-133 (rat, Brazil) Gupta et al. (2009) Anti-arthritic activity of various extracts of Sida rhombifolia aerial parts. Natural Product research: Formerly Natural Product Letters. 23(8):689-695. (rat, India) Jegede IA et al. (2009) Investigation of phytochemical, anti inflammatory and anti nociceptive properties of Ipomoea asarifolia leaves. Journal of Medicinal Plants Research 3(3):160-165. (Rats, Nigeria) Sujatha K et al. (2009) Synthesis, analgesic and anti-inflammatory activities of bis(indolyl)methanes. Indian Journal of Chemistry. 48B(02):267-272. (Rats, India) Bhandari SV et al. (2008) Anti-inflammatory, analgesic, ulcerogenic and nitric oxide releasing of some novel non-steroidal ibuprofen analogs in animal models. Pharmacologyonline 2: 572-587. (Mouse, India)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

49


Analgesia

NEW Dynamic Weight Bearing Test

Measuring the Postural Equilibrium on Freely Moving Rodents Dynamic Weight Bearing Test

Analysis and replay can be performed on-site or remotely. Replaying the experiment with the recorded video file allows the operator to further complement the posture and behavior of the animal, enhancing the interest of the test. During this time, the user can check and secure each limb recognition. The weight distribution of the animal, per limb, is shown in the result window for each time period with the mean and variation coefficient. All data is presented in the Excel file.

Specifications Overall Dimensions (L x W x H cm): Mouse

17 x 17 x 12 cm (6.7 x 6.7 x 4.7 in)

Rat

30 x 30 x 25 cm (11.8 x 11.8 x 9.8 in)

Overall Weight: Mouse

1 kg (2.2 lbs)

Rat

2.5 kg (5.5 lbs)

Power Supply

Key Features

➤ Measure independently the weight bore by each limb of a freely moving animal

➤ Data capture allows for analysis and replay to be performed for user validation of data ➤ Accuracy and resolution insured by an initial calibration

➤ High throughput possible in this minimal stress to the animal hardware

Parameters Measured

➤ Weight bore on each limb, averaged and coefficient of variation ➤ Time period, mean and coefficient of variation

➤ Raw data is encrypted (GLP) and recorded with a sampling rate of 10 Hz including synchronized video recording

Components Included ➤ Animal cage ➤ One sensor

➤ USB interface ➤ Webcam ➤ Software

Dynamic Weight Bearing Test

From PC USB port

Animal Cage Internal Dimensions: Mouse

11.5 x 11.5 x 11.5 cm (4.5 x 4.5 x 4.5 in)

Rat

25 x 25 x 24 cm (9.8 x 9.8 x 9.5 in)

Sensor Accuracy: Mouse

1g

Rat

1g

Sensor Resolution: Mouse

0.2 g

Rat

0.2 g

Sensor Range: Mouse

15 to 100 g

Rat

100 to 500 g

Cage Material: Floor Walls and top cover Computer Requirements

Gray PPC Transparent PPC Pentinum PC 2 Go Ram, Windows® XP/Vista with 2 USB ports minimum

Order # Model

Product

BH2 76-0474 DWB-M

Dynamic Weight Bearing Test, Mouse

BH2 76-0497 DWB-R

Dynamic Weight Bearing Test, Rat

Newly developed, our Dynamic Weight Bearing Test, features a floor instrumented cage. This allows independent measurement of the weight bore by each limb for the freely moving animal. This system accuracy and resolution are ensured via a metrological calibration performed prior to the data capture. During the data capture, the raw data for each paw are synchronized with the images from a video camera and the averaged values are encrypted and recorded on a PC through a USB link along with the sampling rate of 10 Hz.

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Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Analgesia

Incapacitance Meter Incapacitance Tester

The current value of the weight applied on each sensor cell is shown on the LCD display of the LE7950 control unit in a user-selected unit (grams, Newton or oz/lbs). A remote footswitch controls the test start/stop allowing rapid hands-free experiments. The control unit also allows to compute and display statistics (mean, SD) for the groups of animals under test during the measurements. No PC is required for running the Incapacitance Test, although the possibility is given to send collected data from the instrument to a PC through the integrated RS-232 interface SeDaCom.

Specifications

Key Features

➤ Assess spontaneous pain in absence of the application any experimental noxious or non-noxious stimulus ➤ Specially designed animal holders (mouse and rat) to get relevant results more rapidly

➤ Data given using user selected unit (grams, Newton, ounces, or pounds) ➤ Easy and precise instrument

Parameters Measured

➤ Current value of the weight applied on each sensor

➤ Mean value calculated in an user-defined interval of time

Incapacitance Meter The Incapacitance test represents an unsurpassed method for assessing spontaneous pain in laboratory animal model with inflammation or nerve injury in one hind paw (neuropathy, incision etc). Indeed, classic measurements of nociceptive thresholds as used in most of the experimental studies allows assessment of only a pain sensitivity level, not a spontaneous pain level, in the absence of experimental nociceptive stimuli.

Resolution

0.05 gr

Average

1 to 300 seconds

Overpressure

2000 gr

Control Unit Dimensions

17 x 25 x 10 cm

Communications

RS-232 (USB)

Order # Model

Product

BH2 76-0115 LE7900

Incapacitance Test Sensor

BH2 76-0116 LE7920

Incapacitance Test Holder, Mouse

BH2 76-0117 LE7930

Incapacitance Test Holder, Rat

BH2 76-0118 LE7950

Incapacitance Test Control Unit, Includes SeDaCom

Citations Laboureyra E et al. (2009) Long-Term Pain Vulnerability After Surgery in Rats: Prevention by Nefopam, an Analgesic with Antihyperalgesic Properties. Anesth. Analg. 109:623-631. (rat, France) Liu S et al. (2009) Combination of Microsurgery and Gene Therapy for Spinal Dorsal Root Injury Repair. Mol. Ther. 17(6):992-1002. (rat, France) Rivat C et al. (2008) Polyamine deficient diet to relieve pain hypersensitivity. Pain. 137(1): 125-137 (Rat, France) Richebé P et al. (2009) Ketamine Improves the Management of Exaggerated Postoperative Pain Observed in Perioperative Fentanyl-treated Rats. Anesthesiology. 102(2):421-428. (rat, France)

In the incapacitance test, the animal is located in a holder specially designed to maintain the animal comfortably positioned on two separated sensor plates. The Panlab/Harvard Apparatus Incapacitance tester enables then to quantify the spontaneous postural changes reflecting spontaneous pain by independently measuring the weight that the animal applies each hind paw on two separate sensors. In the absence of hind paw injury, rats applied equal weight on both hind paws, indicating a postural equilibrium. After unilateral hind paw tissue injury, a change in the weight distribution on the sensor can be detected, with a lower weight applied by the injured paw.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Analgesia

Pressure Application Measurement Pressure Application Measurement

Pressure Application Measurement The new Pressure Application Measurement (PAM) device offered by Harvard Apparatus is a novel, easy to use tool for measuring mechanical pain threshold in experimental joint hypersensitivity models in rodents. The PAM device has been designed and validated specifically for the mechanical stimulation and assessment of joint pain, and therefore is especially useful in studying arthritis. The PAM device applies a quantifiable force for direct stimulation of the joint and for automatic readout of the response. The operator simply wears a special force sensor on the thumb and measures the force which elicits the animal’s response, normally limb withdrawal.

Key Features

➤ User controlled application of pressure directly to the joint ➤ Automatic recording of limb withdrawal

➤ Resolution of 0.1g (6% maximum gram force) ➤ Maximum gram force up to 1500 grams!

Parameters Measured ➤ Gram force

Components Included ➤ Electronic unit

➤ Joint Transducer, 5mm ➤ Joint Transducer, 8mm ➤ Software

➤ Foot pedal

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Each PAM device comes standard with two force sensors, which have been specially designed to apply force to rat and mouse joints. The area stimulated using the small sensor is 5mm diameter, useful for mice. The large sensor has an 8mm diameter area of contact and is useful in stimulating either mice or rat joints. The electronic unit is compact and connects to the mains power or can be battery-operated for maximum flexibility. The internal batteries for this device may be recharged by USB connection to a PC and recharging occurs simultaneously with its operation. A foot pedal switch is provided for manual score of the peak force applied. The PAM device has an internal memory for data storage and also includes dedicated software.

Order # Model

Product

BH2 72-6172 38500

PAM Pressure Application Device

Citations Barton NJ (2007) Pressure application measurement (PAM): A novel behavioural technique for measuring hypersensitivity in a rat model of joint pain. Journal of Neuroscience Methods. 163, 67-75

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning & Memory Guide Learning refers to the process by which relatively permanent changes occur in behavioral potential as a result of experience. Memory is the process by which the learned information is encoded, stored, and later retrieved. During the two last centuries, the study of learning and memory have been central to three disciplines: philosophy, psychology and biology. These in turn have contributed to highlighting the complexity of these concepts. The most common theoretical classification of memory distinguishes its forms on the basis of information storage duration; short-term memory (properly defined as the ability to store information temporarily, for seconds, before it is consolidated into long-term memory), long-term memory (properly defined as the ability to learn new information and recall this information after some time has passed) and working memory (used to refer to the temporary maintenance of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment).

Another manner to classify forms of memory is based on the nature of the information and how it is aquired. On the one hand, declarative memory involves explicit information about facts and associations with other events, and must be recalled to consciousness to be used. On the other hand, procedural memory is related to the knowledge of rules of action and procedures, which can become automatic and unconscious with repetition. Procedural memory itself is often parceled as associative and non-associative learning. Non-associative learning classically refers to habituation (decreased response to a repetitive presentation of a stimulus) and sensitization (enhanced response to many different stimuli after experiencing an intense or noxious one). In associative (or Pavlovian) learning, an animal learns that two stimuli are associated with each other (classical conditioning) or that a response is associated with a given event/consequence (operant conditioning).

Throughout evolution, mammals have developed such that their brains can acquire and store information about objects and situations, for short and long periods of time, using multiple sensory modalities. As a consequence, behavioral tasks have been developed in laboratory animals, attempting to characterize a number of the different types of information stored and the neuroanatomical structures used to do so. It is necessary to remember that although an experimenter may intend to evaluate a particular form of memory, other memories may interfere or enhance the measures of memory taken. Moreover, learning and memory are multifaceted. As a consequence, a complete understanding of the impact of a particular drug or genetic manipulation cannot be achieved if only one type of behavior or memory system is investigated. The greater the number of behavioral domains tested, the better the understanding of the specific actions of drugs and genes. Memory and learning deficits, which severely alter quality of life, appear with normal aging and are associated with numerous diseases, such as Alzheimer’s Disease, brain damage, Huntington’s Disease, Multiple Sclerosis, Parkinson’s Disease and HIV among others. Studying learning and memory neurobiological mechanisms is therefore essential to find efficient therapeutic strategies. To do so, various behavioral tasks have been developed in laboratory rodents and are largely validated. These are commonly used to assess many aspects of learning and memory abilities in response to drug administration and to study their neurobiological mechanisms.

From a historical perspective, Ivan Pavlov was the first experimenter to research classical conditioning. Starting as a simple physiological experiment with canines, his studies turned out to be the discovery of what is now known as conditioning, more specifically, classical conditioning. James Watson was the pioneer psychology theorist that translated the ideas of Pavlov’s classical conditioning to humans. B.F. Skinner brought a new face into the world of behaviorism with his work on Operant Conditioning, which is very similar to classical conditioning but includes reinforcers. After a response occurs, due to a certain stimulus, reinforcers (positive or negative) are inserted that will increase or diminish the probability that the behavior may occur again.

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Learning & Memory Guide Behavioral Test

Behavioral Test

Passive Avoidance

Active Avoidance

Passive Avoidance paradigms require the subjects to behave contrary to their innate tendencies for preference of dark areas and avoidance of bright ones. The apparatus chamber used in this test is composed of a black and a white compartment. Typically, during the conditioning phase, an aversive stimulus, i.e. a mild footshock, is administered when the subject enters into the dark compartment (conditioning phase). Thus, the conditioned response is given by the avoidance of this compartment while it is more attractive for the subject, in the test phase and memory performance is positively correlated to the latency to enter into the dark compartment.

In the Active Avoidance paradigm, subjects learn to avoid an aversive stimulus by initiating a specific locomotor response. In this task, animals are placed in a two-compartment shuttle box and have to learn the association between a conditioned stimulus (CS, e.g. light) and an unconditioned stimulus (US, e.g. footshock). Subjects give a conditioned response when they avoid receiving the shock, by moving to the opposite compartment during the CS presentation (avoidance response). If animals do not act, a foot shock is delivered, but can be avoided by moving to the opposite compartment (escape response).

Reasons for Choosing This Test ➤ Quick procedure for studying shortand long-term memory ➤ Classical conditioning (stimulus response learning) ➤ Hippocampal independent process ➤ Involves animal inhibiting its behavior in order to avoid shock (different from active avoidance procedures) ➤ Ideal test for first screening ➤ Simple to setup and use ➤ Does not require prior food deprivation ➤ Sensitive for both mice and rats

This test is also used for assessing depressivelike symptoms in animals involved in a “learned helplessness procedure”. In this context, the use of a previously inescapable shock session has profound and long-lasting disruptive effects on the ability of the animals to learn to escape shocks. This escape deficit can be prevented by administering antidepressants.

Reasons for Choosing This Test

➤ Requires footshock administration which can be stressful to the subject

➤ Associative learning (operant conditioning), short- and long-term memory ➤ Provides procedures for testing acquisition, consolidation and retention processes ➤ Gives index of learning progression (evolution curves of performance) ➤ Standard test for Phenotyping ➤ Does not require prior food deprivation ➤ Sensitive for both mice and rats

Related Human Disease/Applications

Reasons for Not Choosing This Test

➤ ➤ ➤ ➤

➤ Requires foot shock administration which can be stressful for the animal ➤ Fear and anxiety influence avoidance ➤ Change in pain sensitivity can interfere with foot shock perception ➤ Locomotor activity alterations can interfere with avoidance/escape responses

Reasons for Not Choosing This Test

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Related Human Disease/Applications ➤ ➤ ➤ ➤

54

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning & Memory Guide Behavioral Test

Behavioral Test

Morris Water Maze

Radial Maze

The Morris Water Maze is the most common test used to evaluate cognitive functions. It is typically used to identify drugs, genetic manipulations, or other experimental conditions that alter spatial memory in rodents. This task uses a circular pool of water in which a small platform is submerged beneath the surface and is based on the innate tendency of rodents to escape from water. Following several trials, when placed in the maze, subjects learn the platform location, using external visual cues. Latency and distance travelled to reach the platform are inversely correlated to memory performance, so are increased in animals with spatial memory impairments. Different kinds of protocols can be used for evaluation of non-spatial memory processes (cued version).

The Radial Maze task utilizes the natural tendency of food-deprived rodents to learn and remember different spatial locations for food in an eight-arm radial maze. The large choice of protocol configurations available in this task have been proven to be very useful in assessing neurobehavioral bases for learning and memory. In the procedure to assess reference memory, only some arms are baited at the beginning of the session. First entry into a non-baited arm constitutes a reference memory error and repeated entries to a baited and non-baited arms are defined as a working memory error.

Reasons for Choosing This Test

Reasons for Choosing This Test

➤ Spatial memory and non-spatial memory, working and reference memory ➤ Gives index of learning progression (evolution curves of performances) ➤ Standard test for Phenotyping ➤ Extremely sensitive to hippocampal lesions and aging ➤ Does not require prior food deprivation ➤ No odor guidance cues ➤ More complex and realistic task compared to a binary choice such as the T or Y maze ➤ Sensitive for both mice and rats

➤ Sensitive for both mice and rats ➤ Spatial memory and non-spatial memory, working and reference memory ➤ Gives index of learning progression (evolution curves of performances) ➤ Robust performance, can be tested across a large range of delays

Reasons for Not Choosing This Test ➤ Requires food deprivation that may represent a major drawback for its use in knock-out mice ➤ Locomotor activity alterations can interfere with arm exploration

Reasons for Not Choosing This Test ➤ Labor intensive experiment ➤ Locomotor activity alterations can interfere with swimming displacements

Related Human Disease/Applications ➤ ➤ ➤ ➤

Related Human Disease/Applications ➤ ➤ ➤ ➤

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Learning & Memory Guide Behavioral Test

Behavioral Test

Spontaneous Alternation

Delayed Alternation Task

The Spontaneous Alternation Task is used to assess spatial working memory in rodents and is based on the innate tendency of rodents to explore a prior unexplored arm or a T- or Ymaze. Thus, a rodent typically remembers which arm it has just visited. Two types of procedures are classically described. In a first procedure, the subject is allowed to freely explore the maze. Alternation behavior, defined as consecutive entries into each of the three arms without repetition, is measured. In another procedure, the subject is placed at the end of the start arm of a T- or Y-maze and is allowed to explore one of the two other arms. The subject is then returned to the start arm and will typically choose to explore the alternate arm, which corresponds to a correct choice.

The Delayed Alternation Task allows assessing spatial working memory in a T- or Y-maze. In the first trial of the test, the animal is placed at the end of the start arm and has to choose between the two other arms that are baited. Once the choice is made, the subject is removed and after a variable delay, is returned to the start arm. In this second trial, the one baited arm is now the opposite arm to which was chosen during the first trial. The animal has to make a different choice than its first one (correct choice) to get the reward.

Reasons for Choosing This Test ➤ Spatial working and reference memory ➤ Simple task (binary choice) ➤ Sensitive for both mice and rats

Reasons for Choosing This Test ➤ ➤ ➤ ➤ ➤ ➤

Spatial and non- spatial working memory Standard test for phenotyping Simple to setup and use Quick procedure Does not require prior food deprivation Sensitive for both mice and rats

➤ Requires food deprivation ➤ May represent a laborious procedure (difficult to automate) ➤ Locomotor activity alterations can interfere with arm exploration

Reasons for Not Choosing This Test

Related Human Disease/Applications

➤ Locomotor activity alterations can interfere with arm exploration

➤ ➤ ➤ ➤

Related Human Disease/Applications ➤ ➤ ➤ ➤

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Reasons for Not Choosing This Test

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning & Memory Guide Behavioral Test

Behavioral Test

Fear Conditioning

Fear Potentiated Startle Reflex

Fear Conditioning is a form of Pavlovian learning that involves making association between stimuli and their aversive consequences. This task is based on the conditioning of a response to fear consisting in a complete lack of movements, i.e. the freezing behavior. During a training phase, the animal is exposed to a conditioned stimulus (tone or light), paired with a mild footshock (unconditioned stimulus). After a delay, the context-dependent fear is evaluated by measuring freezing behavior in subjects replaced in the same apparatus without tone/light presentation.

The Fear Potentiated Startle Reflex test is a paradigm in which amplitude of a simple reflex is increased when presented with a cue that has been previously paired with an aversive stimulus. In the training phase, subjects are exposed to several light footshock pairings in a startle box. Later, in the test phase, acoustic startling stimuli are presented consecutively to the light cue. If the association between the light cue and the foot shocks has been learned correctly in the training phase, light cue prior exposure increases the startle response. Inversely, in subjects with alteration of learning and memory abilities, prior presentation of the light cue does not change the startle response.

Cued-dependent fear is reflected by measuring freezing in response to tone/light presentation in a distinct chamber. These tasks challenge different areas of the brain.

Reasons for Choosing This Test ➤ Associative learning (classical conditioning), short- and long-term memory ➤ Allows assessing memory dependent on hippocampus (contextual fear conditioning) or not (cue-dependent fear conditioning) ➤ Standard test for phenotyping ➤ Conditioning task ➤ Does not require prior food deprivation ➤ Sensitive for both mice and rats

Reasons for Choosing This Test ➤ ➤ ➤ ➤

Associative learning, short- and long-term memory Non-operant procedure Does not require prior food deprivation Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Requires footshock which can be stressful to the animal ➤ Needs intact sensorimotor gating ➤ Fear and anxiety influence the startle response ➤ Change in pain sensitivity can interfere with foot shock intensity perception

Reasons for Not Choosing This Test ➤ Requires footshock which can be stressful for the animal ➤ Fear and anxiety influence the freezing response ➤ Change in pain sensitivity can interfere with foot shock intensity perception

Related Human Disease/Applications ➤ Neurodegenerative Diseases related to Aging ➤ Alzheimer’s Disease ➤ Drug Screening

Related Human Disease/Applications ➤ ➤ ➤ ➤

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

57


Learning & Memory Guide Behavioral Test

Behavioral Test

Object Recognition Test

Social Recognition Test

The Object Recognition Test is based on the natural tendency of rodents to investigate novelty. In the training phase of the task, subjects are allowed to freely explore objects in an experimental arena. After a delay, two objects, including the known one and a novel, are presented to the subject in the test phase. The choice to explore the novel object reflects the use of the recognition memory processes.

The Recognition Test is based on the natural tendency of rodents to investigate a novel congener instead of a familiar one. In this task, a first phase consists in presenting a congener the experimental subject. In a second phase, the experimental subject is exposed to two congeners, including the known one and a novel one. Observations of social interactions classically show that the experimental subject preferentially investigate the unknown congener. This innate tendency involves intact social interactions and memory processes.

Reasons for Choosing This Test ➤ ➤ ➤ ➤ ➤ ➤ ➤

Short- and long-term memory Not dependent upon the hippocampus Less influenced by non-specific locomotor effects Standard test for phenotyping Simple to setup and use Does not require prior food deprivation Sensitive for both mice and rats

Related Human Disease/Applications ➤ ➤ ➤ ➤

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Reasons for Choosing This Test ➤ Allows studying both social and memory processes ➤ Short- and long-term memory for social information and cues that identify individual subjects ➤ Requires amygdale dependent and hippocampal-independent processes ➤ Less influenced by non-specific locomotor effects ➤ Standard test for phenotyping ➤ Simple to setup and use ➤ Does not require prior food deprivation ➤ Sensitive for both mice and rats

Related Human Disease/Applications ➤ ➤ ➤ ➤

58

Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning & Memory Guide Behavioral Test

Behavioral Test

5-Choice Serial Reaction Time Task

DMTP/DNMTP

The 5-Choice Serial Reaction Time (5CSRT) Task is commonly used to evaluate attention performance using visual discrimination in laboratory animals. It represents a conditioning paradigm, involving intact attention processes. In this test, the subject has to learn to respond to a brief illumination of one of the five openings, by poking its nose inside the correct hole in order to obtain a food reward. More the rules are learned by the subject, more the time spent to get the reward, as well as the number of errors are decreased. These parameters give information about the functional integrity of attention and learning processes and are mostly altered in animal models of Schizophrenia and Alzheimer’s Disease.

Reasons for Choosing This Test ➤ Allows studying both social and memory processes ➤ Short- and long-term memory for social information and cues that identify individual subjects ➤ Requires amygdale dependent and hippocampal-independent processes ➤ Less influenced by non-specific locomotor effects ➤ Standard test for phenotyping ➤ Simple to setup and use ➤ Does not require prior food deprivation ➤ Sensitive for both mice and rats

The Delayed-Matching to Position/Not-toPosition Task measures the ability of subjects to learn a rule in which they have to associate the position of a stimulus previously presented and an action for getting a reward. At the start of each trial, one of two retractable levers is presented to the subject while in an operant chamber. The subject has to press the lever for indicating that the sample has been registered. After a delay (fixed or variable), both levers are presented simultaneously. In the DMTP version of the task, the subject has to press the same sample lever as the one presented before the delay to receive the reward, whereas in the DNMTP version, the subject has to press the opposite lever. The number of correct responses indicates the subject’s learning and memory performance.

Reasons for Choosing This Test ➤ Short- and long-term memory, procedural and spatial working memory ➤ Operant conditioning ➤ No olfactory or spatial uncontrollable cues ➤ Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Requires prior food deprivation ➤ Influenced by non-specific effects on attention processes

Reasons for Not Choosing This Test ➤ Classically used in rats and more recently adapted for mice ➤ Long and laborious procedure ➤ Requires prior food and drink deprivation ➤ Changes in behavioral output can be brought by many non-cognitive factors, such as alteration of locomotor activity, vision, anxiety level

Related Human Disease/Applications ➤ Neurodegenerative Diseases related to Aging ➤ Alzheimer’s Disease ➤ Drug Screening

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

Attention-Deficit Hyperactivity Disorder (ADHD) Schizophrenia Autism Neurodegenerative Diseases related to Aging Alzheimer’s Disease Drug Screening

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

59


Learning & Memory Guide Behavioral Test

Behavioral Test

Social Interaction Test

Social Transmission of Food Preference Test

The social interaction test by pairs provides a popular and standard paradigm to study general social behavior. This test consists in allowing the experimental subject freely exploring an unfamiliar congener in its home cage or in a neutral environment. Social exploration is measured by the time spent by the experimental subject around the congener as well as the amount and duration of behaviors that compose social interaction (e.g. sniffing, following, grooming, biting, mounting, wrestling…). Social avoidance behavior is used in a wide variety of models, for instance, for assessing neophobia anxiety and depression-like behavior.

Social transmission of food preference is a test that is used in rodents to assess memory processes as well as social interaction ability. This test is based on the fact that rodents are able to learn about potential food sources by sampling those sources on the breath of liter mates. This task requires a demonstrator, previously exposed to a scented food, which interacts with an observer to transmit its food exposure experience. If social transmission of food preference has occurred, the observer will preferentially consume the same diet that was fed to the demonstrator when confronted with a choice.

Reasons for Choosing This Test ➤ Classic social interaction test widely used in literature ➤ Can be completed quickly ➤ Simple to setup and use ➤ Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Difficult to automate

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤ ➤

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Drug Screening Phenotyping Autism Schizophrenia Neophobia Anxiety Depression

Reasons for Choosing This Test ➤ Allows studying both social and memory processes ➤ Evaluates ability to learn about the safety of food from its fellow liter mates ➤ Assessing long-term odor memory and consolidation studies ➤ Does not require exposure to aversive stimuli ➤ Standard test for phenotyping ➤ Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Influenced by non-specific effects on olfaction

Related Human Disease/Applications ➤ Alzheimer’s Disease ➤ Drug Screening ➤ Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Attention Guide

Attention is fundamental to the processing of information that occurs during learning and memory. Attentional processes enable subjects to efficiently perceive or focus on certain environmental stimuli and to ignore others. Attention is not a unitary concept and consists of several distinct mechanisms: • SUSTAINED ATTENTION (OR VIGILANCE): A continuous focus for the detection of rare events • DIVIDED ATTENTION: Several stimuli are simultaneously monitored • SELECTIVE (FOCUSED) ATTENTION: Focus on a restricted number of stimuli, while ignoring the rest

In practice, many situations require a mixture of these different processes. Impairments of attention processes result in severe cognitive and behavioral dysfunctions and are found in various pathologies, In particular in attentiondeficit/hyperactivity disorder (ADHD), the most commonly psychiatric disorder of childhood. Moreover, deficits in attention are commonly associated with schizophrenia, autism and with age-related decline of memory performances. Whereas attention processes have largely been characterized in humans, experimental studies of neurobiological mechanisms in humans are limited. In this way, various behavioral tests used in humans have been developed in animals, in particular in laboratory rodents, allowing advances in attention-relative knowledge and growth of efficient therapeutic strategies.

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Attention Guide Behavioral Test

Behavioral Test

5/9 Holes Box

Startle Reflex

The 5-Choice Serial Reaction Times (5CSRT) task is commonly used to evaluate attention performance using visual discrimination in laboratory animals. It represents a conditioning paradigm, involving intact attention processes. In this test, the subject has to learn to respond to a brief illumination of one of the five openings, by poking its nose inside the correct hole in order to obtain a food reward. 5-Choice Serial Reaction Time Test: The more the subject learns the rules, the more time they spend obtaining the reward and also the number of errors are decreased. These parameters give information about the functional integrity of attention and learning processes and are mostly altered in animal models of schizophrenia and Alzheimer’s disease.

Prepulse Inhibition (PPI) paradigm is commonly used to evaluate sensorimotor gating as well as attention processes involved in information selection processing. The startle response is a brainstem reflex elicited by an unexpected acoustic or tactile stimulus. In the prepulse inhibition test, sensorimotor gating is assessed by evaluating the characteristics of the innate reduction fo the startle reflex induced by a weak pre-stimulus. This test measures preattentive processes that operate outside of conscious awareness and is widely used in animal models of diseases marked by inability to inhibit or “gate” irrelevant information in sensory, motor or cognitive domains.

Reasons for Choosing This Test

➤ Resproduces the same paradigm used in humans to detect attention and sensorimotor gating disorders ➤ Objective measurement: automated detection fo startle reflex ➤ Sensitive for both rats and mice

➤ Widely used in literature to study visual discrimination and attention ➤ Involves associative learning, procedural memory and operant conditioning ➤ Allows the exploration of a wide variety of cognitive processes ➤ Robust performance and specific responses

Reasons for Not Choosing This Test ➤ Classically used in rats and more recently adapted for mice ➤ Long and laborious procedures ➤ Requires prior food and drink deprivation ➤ Changes in behavioral output can be brought by many non-cognitive factors, such as alteration of locomotor activity, vision, and anxiety level

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

62

Attention-Deficit Hyperactivity Disorder (ADHD) Schizophrenia Autism Neurodegenerative diseases related to aging Alzheimer’s Drug Screening

Reasons for Choosing This Test

Reasons for Not Choosing This Test ➤ Restraint conditions (habituation phase needed) ➤ Influenced by non-specific effects on sensorimotor gating

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤

Drug Screening Phenotyping Attention-Deficit Hyperactivity Disorder (ADHD) Schizophrenia Autism Obsessive compulsive disorder Huntington’s Disease Nocturnal enuresis Tourette Syndrome

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention Shuttle Box for Active and Passive Avoidance Components Included ➤ Active Box (Shuttle Box)

➤ Control Unit with RS-232 communication port ➤ SeDaCom software

➤ Cables and connectors ➤ Instruction manual ➤ 2 year warranty

Options

➤ Motorized door to convert Active Box into Passive Box ➤ Sound Attenuating Box

➤ LE2708 avoidance programmer including shocker

➤ ShutAvoid software to control up to 8 active or passive boxes ➤ LE10026 shocker unit with scrambler (0-2mA output)

Shuttle Box Key Features

➤ Highly sensitive weight transducer system for accurate animal detection ➤ Easy to set up different wall shapes and colors

➤ Optional guillotine door for passive avoidance ➤ Compartments with independent grid floor

➤ Front and top doors for easy access inside the box

➤ Up to 8 active boxes can be controlled simultaneously from one PC ➤ Neither PC interface nor PC cards are required

➤ Safety system which guarantees that the shock intensity received by the animal is always the same value independently of the grid bars treaded

Parameters Measured

➤ Latency to entrance into the black compartment (passive avoidance) ➤ Number and latency of conditioned responses (active avoidance)

➤ Number and latency of unconditioned responses (active avoidance)

➤ Number and latency of null responses (active avoidance)

➤ Number and latency of none responses (active avoidance)

Panlab/Harvard Apparatus Shuttle Boxes LE916 (Rats) and LE918 (Mice) provide the ideal environment to carry out conditioned reflexes (Active and Passive Avoidance) in learning and memory studies. The Shuttle Box (LE916-918) consists of two equally sized compartments with two independent grid floors. A front door, in addition to the top ones, allows an easy access inside the box. The cage contains a general sound generator and a visual stimulus (light) for each compartment. The animal is detected by two weight transducers located above the static grids, avoiding the problems inherent to photoelectrical or grid tilting systems (high speeds of displacements in mice, tail detection in rats). Our Shuttle Box is thought to be easily set up and dismantled. Therefore, reconverting it to traditional Passive Box is quite straightforward by adding a sliding door (LE916D for mice or LE918D for rats). It is also possible to set up different wall shapes or colors in order to further condition the subject of study either visually or spatially. The Shuttle Boxes can be controlled by Programmer LE2708 or our software, ShutAvoid. SeDaCom software is included for transferring data from the programmer to a PC through a RS-232 port. The connection is direct between the programmer and PC. No PCI card is needed! The link is carried out by one only cable from one box to the other. The first box is connected to PC or laptop by the RS-232 port or USB. The second option is suitable for controlling a number of boxes simultaneously.

➤ Number of compartment changes during the intertrial intervals (active avoidance) ➤ Latency mean and accumulated responses sorted by interval of time

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Learning, Memory & Attention

Shuttle Box for Active and Passive Avoidance (continued) Specifications Cage Dimensions: LE916 Rat

510 (W) x 250 (D) x 240 (H) mm internal; 580 x 360 x 305 mm external

LE918 Mouse

590 (W) x 190 (D) x 240 (H) mm internal; 580 x 360 x 305 mm external

Minimum Weight Detected

10 grams (Mouse Box); 40 grams (Rat Box)

Material Composition

Methacrylate, aluminum, stainless steel

Computer Requirements (withSeDaCom)

PC (Windows® 95, 98, ME, NT, 2000, XP and Vista)

Maximum Number of Stations (with ShutAvoid)

8 stations connected to a PC

Connection of Several Units to PC

Neither PC interface nor PC card are required. One cable connects all units to the PC

Certifications

CE compliant

Power Supply

110 V/220 V, 50/60Hz

Order # Model

Product

BH2 76-0250 LE916

SHUTTLE BOX with Static Floor (Needs Shocker) Rat

BH2 76-0251 LE918

SHUTTLE BOX with Static Floor (Needs Shocker) Mouse

BH2 76-0157 LE26

Sound Attenuating Box

BH2 76-0252 LE916D

Guillotine Door for Rat Shuttle Box LE916 and Make it Capable to Run Passive Avoidance Experiments

BH2 76-0253 LE918D

Guillotine Door for Mouse Shuttle Box LE918 and Make it Capable to Run Passive Avoidance Experiments

BH2 76-0201 LE2708

AVOIDANCE PROGRAMMER with Shocker

BH2 76-0202 SHUTAVOID

PC SOFTWARE to Control up to 8 Active/Passive Boxes

BH2 76-0159 LE10026

Shock Generator with Scrambler, 0-2 mA Output

OPTIONS

64

Citations Dagnino-Subiabre A et al. (2009) Chronic stress induces dendritic atrophy in the rat medial geniculate nucleus: Effects on auditory conditioning Behavioural Brain Research 203(1):88-96 (rat, Chile) Johannesson M et al. (2009) A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: The NIH heterogeneous stock. Genome Res. 2009 19: 150158. (Rat, Spain, Sweden, UK, USA) Lopez-Aumatell R et al. (2009) Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat strains. Behav. Brain. Res. 202(1):92-101. (active avoidance, rat, Spain) Mendez M et al. (2009) Associative learning deficit in two experimental models of hepatic encephalopathy. Behav. Brain Res. 198(2):346-351. (active and passive avoidance, rat, Spain) Valverde O et al. (2009) GPR3 receptor, a novel actor in the emotional-like responses. PLoS One. 4(3):e4704. (mice, Spain, Belgium) Martin-Garcia et al (2008) Neonatal finasteride induces anxiogenic-like profile and deteriorates passive avoidance in adulthood after intrahippocampal neurosteroid administration. Neuroscience. 154(4):1497-1505 (rat, Spain) Mendez et al. (2008) Associative learning deficit in two experimental models of hepatic encephalopathy. Behavioural Brain Research, Volume 198, Issue 2, 17 March 2009, Pages 346-351. (Rat, Spain) Rueda N et al. (2008) Effects of chronic administration of SGS-111 during adulthood and during the pre- and post-natal periods on the cognitive deficits of Ts65Dn mice, a model of Down syndrome. Behavioural Brain Research, Volume 188, Issue 2, 9 April 2008, Pages 355-367 (mice, Spain) Ruiz-Medina J et al (2008) Intracranial self-stimulation improves memory consolidation in rats with little training. Neurobiol. Learn. Mem. 89(4):574-581 (rat, Spain) Trigo JM et al (2008) MDMA modifies active avoidance learning and recall in mice. Psychopharmacol. 197:391-400 (mouse, Spain) Andero R et al. (2007) Electrical stimulation of the pedunculopontine tegmental nucleus in freely moving awake rats: Time- and site-specific effects on two-way active avoidance conditioning. Neurobiol. Learn. Mem. 87(4):510-521 (rat, Spain) Bura SA et al. (2007) Genetic and pharmacological approaches to evaluate the interaction between the cannabinoid and cholinergic systems in cognitive processes. Br J Pharmacol. 2007 March; 150(6): 758–765. (mice, Spain, Belgium) Quiroz-Padilla MF et al. (2007) Effects of parafascicular excitotoxic lesions on two-way active avoidance and odor-discrimination. Neurobiol. Learn. Mem. (rat, Spain) Lopez-Aumatell R et al. (2007) Fearfulness in a large N/Nih genetically heterogeneous rat stock: Differential profiles of timidity and defensive flight in males and females. Behav. Brain Res. 188(1):4155 (rat, Spain) Millan M et al. (2007) A preferential dopamine D3 versus D2 receptor antagonist and potential antipsychotic agent. III. Actions in models of therapeutic activity and induction of side-effects. J. Pharmacol. Exp. Ther. (rat, France) Soriano-Mas C et al. (2007) Intracranial self-stimulation after memory reactivation: Immediate and late effects. Brain Res. Bull. 74(1-3):51-57 (rat, Spain) Bura SA et al. (2007) Genetic and pharmacological approaches to evaluate the interaction between the cannabinoid and cholinergic systems in cognitive processes. Br. J. Pharmacol. 150(6): 758-765. (active avoidance, mouse, Spain).

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention

ShutAvoid Software for Active & Passive Avoidance Components Included

➤ Software CD with USB protection key ➤ Cables and connectors ➤ Instruction manual

➤ Free software updates of the acquired system

Related Hardware

➤ Shuttle Box, see pages 63 – 64

➤ Passive Avoidance Box, see pages 80 – 81

SHUTAVOID Software SHUTAVOID software is an implemented version of the Panlab/Harvard Apparatus SHUTTLE-8 software offering a user-friendly interface to conduct Active and Passive Avoidance procedures in an automated manner.

software species is hardware specific

Key Features

➤ Good for both Active and Passive Avoidance

➤ Experimental chambers can be controlled independently ➤ Our unique test mode enables immediate and reliable box checking

➤ The program runs automatically when the animal is detected in the cage ➤ Animal position and current data can be visualized online ➤ Provides integrated data

➤ Analyze data in user-defined intervals of time

Parameters Measured

➤ Number and latency of conditioned responses (Active Avoidance)

➤ Number and latency of unconditioned responses (Active Avoidance)

➤ Number and latency of null responses (Active Avoidance) ➤ Number and latency of responses during intertrial (Active Avoidance)

➤ Number of compartment crossing during the intertrial interval (Active Avoidance)

The Software SHUTAVOID controls up to 8 Shuttle Boxes or Passive Cages independently. The software detects how many cages are physically present and activates the corresponding windows. The system includes a test mode to enables immediate and reliable checking of the box features to ensure all of the elements of the experimental chamber are functioning. The program controls the presentation of visual and acoustic stimuli and shock duration, at the same time that it records the position of the experimental animal in each compartment of the experimental cage, deciding about stimuli presentation accordingly. Unlimited number of schedules can be defined and used either by common or different experimental cages. The protocol editor allows the configuration of all the basic parameters necessary to set an active and passive avoidance experiment: habituation period, duration of the inter-trial interval (fixed or randomized), activation and duration of the conditioned stimulus (light, sound or both), activation, latency and duration of the unconditioned stimulus (electrical shock), latency for considering the response as “null”, door status (open/closed), number of trials, cut-off time for response etc… The program runs automatically when the animal is detected in the cage (independently for each cage). During the acquisition of data, information about the protocol state, animal position and current data can be visualized for each cage on the corresponding control window. Data related to each of the observed animal responses are stored into result files that pick up the information acquired during the working session. The data files can be open and re-analyzed to generate ASCII-coded reports in which the information is summarized for each trial or groups of trials (user-defined).

➤ Mean of the responses latencies (Active Avoidance) ➤ Latency to enter into the black compartment (Passive Avoidance)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

65


Learning, Memory & Attention

ShutAvoid Software for Active & Passive Avoidance (continued) Specifications Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM, 1 free USB for the protection key; 1 free RS-232 serial port for boxes connection (a USB-Serial adapter included in the software pack can be used when a RS-232 serial port is not available)

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

System Requirements

Windows® XP (SP2 or Higher), Vista 32

Order # Model

Product

BH2 76-0202 ShutAvoid

PC Software to Control up to 8 Shuttle Boxes or Passive Avoidance Boxes

Citations Dagnino-Subiabre A et al. (2009) Chronic stress induces dendritic atrophy in the rat medial geniculate nucleus: Effects on auditory conditioning. 203(1):88-96. (fear conditioning, rat, Chile, USA) Johannesson M et al. (2009) A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: The NIH heterogeneous stock. Genome Res. 19:150-158. (rat, Spain) Lopez-Aumatell R et al. (2009) Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat strains. Behav. Brain. Res. 202(1):92-101. (active avoidance, rat, Spain) Mendez M et al. (2009) Associative learning deficit in two experimental models of hepatic encephalopathy. Behav. Brain Res. 198(2):346-351. (active and passive avoidance, rat, Spain) Martin-Garcia et al (2008) Neonatal finasteride induces anxiogenic-like profile and deteriorates passive avoidance in adulthood after intrahippocampal neurosteroid administration. Neuroscience. 154(4):1497-1505 (rat, Spain)

66

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention

Circular Pool for Evaluating Learning and Memory Circular Pool

Circular Pool

Morris Water Maze is for spatial working memory studies. The circular pool is manufactured in polypropylene and stands on a support with four wheels for easier displacement. Panlab/Harvard Apparatus proposes a complete solution for water maze settings since the heater, the water circulation pump, the level controller and the electro valve for pool filling are containing in a unique control box. The level controller acts directly on the electro valve, turning it off when the liquid arrives to the corresponding height. The water temperature is thermostated between 22°C and 32°C depending on the environmental room temperature. Two easily interchangeable platforms are supplied (80 and 110 mm) that can be located anywhere in the pool. For Aquatic Radial Water Maze, a removable-floating eight radial-arm maze structure and associated platforms can be provided upon request. Atlantis

Both Morris and Radial Water Mazes may be associated with our VideoTracking Systems for detection and analysis of animal displacements and behavior throughout the test. Please refer to chart below.

Parameter Measured

Video Tracking System Suggested

Latency Time to Raise the Target/Platform

SMART & Smart JUNIOR

Permanence Time and Distance Travelled in Quadrants

SMART & Smart JUNIOR

Total Distance Travelled

SMART & Smart JUNIOR

Latency Time to the First Entrance to Target/Platform

SMART & Smart JUNIOR

Target/Platform Crossings

SMART & Smart JUNIOR

Resting/Floating Time with User-Defined Threshold

SMART & Smart JUNIOR

Key Features

Stopping Time on Target/Platform

SMART

Wishaw's Error

SMART

➤ Complete system, all in one station (water pump, thermostat and tubing all included)

Mean Directionality

SMART

Average Distance to Target/Platform

SMART

➤ Control box controlling the water temperature (thermostated between 22-32˚C depending of the environmental conditions)

Chronological Sequence of the Visits in the Zones

SMART

➤ Support with 4 wheels for better displacement

Permanence Time in Each Arm

SMART

Number of Entries Into Each Arm

SMART

Distance Travelled in Each Arm

SMART

And Other Integrated Parameters Not Directly Related to Water Maze Experiment

SMART

➤ Polyproylene pool

➤ Easily adaptable platform size depending of the animal size ➤ Ideal environment to carry out the Morris and Aquatic Radial Maze studies

Components Included

➤ Circular pool with support (with wheels for easier displacement) ➤ Water pump

➤ Heater, electro valve and level controller ➤ Set of 2 target islands ➤ Set of 2 spare fuses ➤ Instruction manual ➤ 2 year warranty

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

67


Learning, Memory & Attention

Circular Pool for Evaluating Learning and Memory (continued) Specifications Heater Intensity

3000 W

Heating Speed

3° celsius / hour (model LE820-200)

Temperature

22-32 degrees celsius (depending on environment)

Power Requirements

110/220 V / 50Hz

Certifications

CE compliant

Order # Model

Product

BH2 76-0020 LE820-90*

Circular Pool; 90 cm (D) 50 cm (H)

BH2 76-0021 LE820-120*

Circular Pool; 120 cm (D) 60 cm (H)

BH2 76-0022 LE820-140*

Circular Pool; 140 cm (D) 60 cm (H)

BH2 76-0023 LE820-170*

Circular Pool; 170 cm (D) 60 cm (H)

BH2 76-0024 LE820-200*

Circular Pool; 200 cm (D) 60 cm (H)

* Including Heater, water pump, level controller, electro valve and LE820-500 Island Se

OPTIONS

BH2 76-0025 LE820-500

Island Set (110 and 80 mm Diameter Platforms)

BH2 76-0026 LE820-300

Automatic Island 'Atlantis' (controlled by Smart Video Tracking Software)

BH2 76-0027 LE772 BH2 76-0028 SMART

Aquatic Radial Maze Advanced Video-Tracking Software*

BH2 76-0029 SMART JUNIOR Standard Video-Tracking Software * Requires BH2 76-0501 Frame Grabber Board

Citations Arqué G et al. (2008) Impaired Spatial Learning Strategies and Novel Object Recognition in Mice Haploinsufficient for the Dual Specificity Tyrosine-Regulated Kinase-1A (Dyrk1A). PLoS ONE 3(7): e2575. (water maze, mouse Spain) Ruiz-Medina J et al. (2008) Intracranial self-stimulation facilitates a spatial learning and memory task in the Morris water maze. Neuroscience. 154(2): 424-430. (water maze, rat, Spain) Zhang T et al . (2007) Impairments in water maze learning of aged rats that received dextromethorphan repeatedly during adolescent period. Psychopharmacol. 191(1):171-179 (rat, South Korea) Cho HJ et al. (2006) Repetitive dextromethorphan at adolescence affects water maze learning in femal rats. Int. J. Neurosci. 116(2): 91-101 (water maze, rat, Korea) Zhang TY et al. (2006) Impairments in water maze learning of aged rats that received dextromethorphan repeatedly during adolescent period. Psychopharmacol. 5 in process (water maze, rat, South Korea) Gimenez-Llort L et al. (2005) Mice lacking the adenosine A1 receptor have normal spatial learning and plasticity in the CA1 region of the hippocampus, but they habituate more slowly. Synapse. 57(1): 8-16. (mouse, Spain, USA, Sweden) Calza L et al. (2003) Neural stem cells and cholinergic neurons: regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor. PNAS 100(12): 7325-7330. (rat, Italy) Anisman H and McIntyre DC (2002) Conceptual, spacial, and cue learning in the morris water maze in fast or slow kindling rats: attention deficit comorbidity. J. Neurosci. 22(17):7809-7817. (rat, Canada) Altafaj et al. (2001) Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome. Human Mol. Genetics 10(18): 1915-1923. (Morris water maze, mouse, Spain) Wickman K et al. (2000) Brain localization and behavioral impact of the G-protein-gated K+ channel subunit GIRK4. J. Neurosci. 20(15): 5608-5615. (mouse, USA)

68

Economy Circular Pools Harvard Apparatus also offers an economy line of circular pools. These economy models feature: •

Pools nested in a custom swivel caster cart with wheel brakes

Elevated to make the pool more accessible

Side drains for quick emptying and clean up

Island set included - 4" diameter x 12" height

Order # Model

Product

BH2 72-6055 60135

Economy Water Maze, Mouse (4 ft diameter)

BH2 72-6056 60136

Economy Water Maze, Mouse/Rat (5 ft diameter)

BH2 72-6059 60235

Economy Water Maze, Rat (6 ft diameter)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention

Radial Maze for Evaluating Working and Reference Memory A water version of our Radial Maze is also available (see our circular pool product pages 67 and 68 - or contact us for more details).

Radial Maze

Key Features

➤ Allows automated standard experiments

➤ Different possibilities of control for opening and closing the doors (manual or automated)

Parameter Measured

Monitoring System Suggested

Chronological sequence of animal positioning in the radial maze

MazeSoft-8 and SMART

Time of entry in each zone

MazeSoft-8 and SMART

Current position

MazeSoft-8 and SMART

Total number of entries in each zone

MazeSoft-8 and SMART

Total number of reference and working memory

MazeSoft-8 and SMART

Other integrated parameters: number of visits into the arms, response latency, etc…

MazeSoft-8

Specifications

➤ Different possibilities for animal detection (photoelectric cells or video-tracking)

Radial Maze Dimensions:

Components Included

Position Detection Technique

IR beams in the arms, weight cell in the central island or SMART Video Tracking

➤ LE766/8 Control unit (except LE760 and LE762)

Sliding Doors Operation

Manually or automated w/MAZESOFT-8 or SMART

➤ PCI interface (only when LE766/8 in combination with MAZESOFT-8 or SMART)

Material Composition

Methacrylate, aluminum, stainless steel

Aquatic Radial Maze Dimensions

138 (W) x on request (D) x 250 (H) mm

➤ Tripod

Power Requirement

110/220 V, 50/60 Hz

Certifications

CE compliant

➤ Mounted on a tripod of adjustable height ➤ Radial Maze

➤ 8 food baskets (one at each arm's end) ➤ 2 year warranty

Radial Maze

Our Eight Arms Radial Maze is extensively used in behavioral laboratories for evaluating spatial memory but also non-spatial memory associated with motivational cues (classically food). The Panlab/Harvard Apparatus Radial Maze consists in a central area with eight sliding doors giving access to eight equally-sized arms. The maze, made of black plexiglas, is mounted on a tripod with adjustable height (1m max). Each arm has lateral walls with a height higher on the proximal side of the arm than on the distal side. On the distal extreme of each arm, a detachable recessed cup can be installed or replaced by cover (all included). The sliding doors can be opened and closed manually or automatically, with two options in both cases. •

Manual doors operation can be made by the user in-site, by means of a mechanical thread system with pulley or off-site, by using a control unit with eight switches, one for each sliding door.

Automated doors operation can be controlled by the animal position throughout the test using the MAZESOFT-8 software associated with photoelectrical cell mounted on the Radial Maze and the corresponding control units, or using the SMART Video-Tracking System.

Rat

(W) x 1690 (D) x 1250/1450 (H) mm

Mouse

(W) x 867 (D) x 1250/1450 (H) mm

Order # Model

Product

BH2 76-0227 LE760

Standard Radial Maze, Rat

BH2 76-0228 LE762

Standard Radial Maze, Mouse

BH2 76-0229 LE767*

Automated Radial Maze, Rat with SMART

BH2 76-0230 LE769*

Automated Radial Maze, Mouse with SMART

BH2 76-0231 LE766

Automated Radial Maze, Rat (requires MAZESOFT-8)

BH2 76-0232 LE768

Automated Radial Maze, Mouse (requires MAZESOFT-8)

BH2 76-0027 LE772

Aquatic Radial Maze (To Be Used Along with Circular Pool, Must be Ordered Separately)

* Includes PCI7200 when SMART is to control the sliding doors

OPTIONS

BH2 76-0028 SMART

SMART Video-Tracking Software

BH2 76-0144 MAZESOFT-8

MAZESOFT-8 Software

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

69


Learning, Memory & Attention MAZESOFT-8 Software for Learning and Memory MAZESOFT-8 Software MAZESOFT-8

MAZESOFT-8 is complete and easy-to-use software for monitoring radial maze experiments. It has been specially designed to work with the Panlab/Harvard Apparatus Radial Maze and is equipped with rows of infrared photocells for the automated detection of animal position. The software allows for the full control of the arm doors either manually (by means of a button panel in the computer screen) or automatically, when a trained subject is being tested.

software species is hardware specific

Key Features

➤ Complete and easy to-use for standard experiment

➤ Use of photoelectrical cell technology for animal position detection ➤ Manual or automatic control of the doors

➤ Provides integrated parameters (number of errors, number of distinct arms visited, etc)

➤ Data reports can be reorganized according to factors entered in the trial header (animal, groups, etc) ➤ Data exportation to Excel

Parameters Measured

➤ Duration of the experiment

➤ Current position of the animal

➤ Number of working memory errors (repeated “visit” in the baited arms) ➤ Number of reference memory (number of “visit” in the unbaited arms) ➤ Total number of visited arms

➤ Response latency (total duration of the experiment / total number of visited arms) ➤ Number of different arms visited during the experiment (between 0 and 8)

In MAZESOFT-8, the maze is virtually divided into 17 sections: 8 equally sized arms (each one divided into proximal and distal section) and a central area. One experiment can be composed of several trials, depending on the number of experimental groups and animals per group used in the study. The system considers an arm being visited when the subject has been detected in the distal part of the arm. During each trial, the elapsed time, permanence time in each area and current position of the animal can be visualized in real-time. Real-time information about the animal position and the number of visits made are also graphically shown on the screen. A Runtime data panel shows the cumulated number of working and reference memory errors together with other important data (response latency, number and list of visits and entries into the arms etc.) MAZESOFT-8 provides a summary data table containing the complete information about each session (subject name, group, date) together with all the integrated data of interest. The tables of session can be reorganized before exportation according to parameters previously entered in the trial header (by subjects, by groups, by experimenter, etc). Data from the summary database as well as the detailed chronological listing of the animal positions for each session can be easily exported to Excel.

Specifications

➤ Number of arms visited until an 'error' (last arm visited included)

Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM with PCI 32-bit bus master expansion slot available and 1 free USB for the protection key.

➤ List table showing the chronological order of the entries into the different zones of the radial maze

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true colour RGB display.

System Requirements

Windows® XP (SP2 or Higher), Vista 32

➤ List table showing the chronological order of the visited arms and entries into the arms

Components Included ➤ Software CD and USB protection key ➤ PCI-7200

➤ Cables and connectors ➤ Instruction manual

70

MAZESOFT-8 allows the user setting any of the standard protocols for the study of working and reference memory in laboratory animals. The protocols are easy to configure, the user only has to enter some important parameters: designation of the baited arms, conditions to stop the experiments, time-interval between each trial, doors monitoring mode, criterion for considering the arm visited. Each protocol configuration can be saved and opened for use when necessary. A “trial header” can be use for recording all the necessary information associated with the current experiment (code of trial, experimenter, challenge, dose, subject identification, comments).

Related Hardware

➤ Radial Maze, see page 69

Order # Model

Product

BH2 76-0144 MAZESOFT-8

MAZESOFT-8 Software

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention Startle and Fear Combined System Startle and Fear Combined System

Options

➤ Shock Generator ➤ Air Puff Unit

Key Features

➤ STARTLE Software

➤ Combined system for startle/freezing

➤ FREEZING Software

➤ Combined system for mice/rats

➤ Weight transducer sensitivity optimized

➤ Different spacial context configurations available for fear conditioning paradigms ➤ Accurate and traceable data

➤ No PCI cards required - has USB connection, one cable links all!

Parameters Measured

Startle and Fear Combined System The StartFear Combined system is a polyvalent system for conducting both fear conditioning and startle reflex experiments in one enclosure, regardless of the species (from 15 g to 500 g). The StartFear system allows recording and analysis of the signal generated by the animal movement through our unique high sensitivity weight transducer system.

➤ Time of experiment at which each inactivity event has occurred (FREEZING) ➤ Duration of each inactivity event (FREEZING)

➤ Summary table of the total amount of freezing in each state of the experiment (FREEZING)

The analog signal is transmitted to the FREEZING and STARTLE software modules through the load cell unit for recording purposes and posterior analysis in terms of activity/immobility (FREEZING) or startle response characterization (STARTLE).

➤ Maximum amplitude of startle response (STARTLE)

An additional interface associated with corresponding hardware allows controlling the stimuli (light, sounds, shock, air puff) from the STARTLE and FREEZING software modules.

➤ Number and duration of freezing episodes in each user-defined intervals of time (FREEZING) ➤ Latency until the maximum amplitude of startle response (STARTLE) ➤ Duration of the startle response (STARTLE)

➤ Latency until the beginning of the startle response (STARTLE) ➤ Average of the startle response (STARTLE)

➤ Mean startle values for each trial type (STARTLE)

The StartFear cage is made with black methacrylate walls and a transparent front door. In fear conditioning experiment, the walls, cover and floor can be of different materials or colors. A transparent cylinder can be placed into the experimental chamber in order to modify the contextual spatial perception of the subject during the test phase.

Components Included ➤ Experimental Chamber ➤ Sound Proof Box

➤ Load cell amplifier ➤ Station interface

➤ Instruction manual ➤ 2 year warranty

Panlab | Harvard Apparatus

• Spain

+34934190709

Harvard Apparatus +34834750697 •

• International

508.893.8999 • toll free U.S. 800.272.2775 +34934750699 • www.panlab.com

• phone fax

• fax

71


Learning, Memory & Attention Startle and Fear Combined System (continued) Specifications Chamber Dimensions

250 (W) x 250 (D) x 250 (H) mm

Material Composition

Methacrylate, aluminum, stainless steel

Maximum Number of Stations

8 stations connected to a PC

Sounds Frequency and Amplitude

PrePulse/pulse: adjustable from 200 to10000 Hz max 120 dB; white noise: from 60 to 120 dB

Certifications

CE compliant

Power Supply

110 V/220 V, 50/60Hz

Soundproof Box Dimensions

670 (W) x 530 (D) x 550 (H) mm

Order # Model

Product

BH2 76-0280 LE116

FREEZING AND STARTLE Threshold Sensor including Sound Attenuating Box

BH2 76-0235 LE117M

Mouse Holder for Startle Reflex (Animal Weight Required)

BH2 76-0236 LE117R

Rat Holder for Startle Reflex (Animal Weight Required)

BH2 76-0281 LE111

Load Cell Amplifier (One for Each Chamber)

BH2 76-0282 LE118

Stimuli Interface Unit (1 Chamber)

BH2 76-0283 LE1188

Stimuli Interface Unit (up to 8 Chambers)

BH2 76-0284 STARTLE

Software to Control up to 8 Stations for Startle Reflex Studies

BH2 76-0099 FREEZING

Software to Control up to 8 Stations for Fear Conditioning Studies

BH2 76-0404 FREEZINGGLP

Freezing SW-GLP

BH2 76-0159 LE10026

Shock Generator with Scrambler, 0-2 mA Output

BH2 76-0286 LE119

Air Puff Unit

BH2 76-0328 LE115

Contextual Kit for Fear Conditioning

OPTIONS

72

Citations Viosca J et al. (2009) Enhanced CREB-dependent gene expression increases the excitability of neurons in the basal amygdala and primes the consolidation of contextual and cued fear memory. Learn Mem. 16(3):198-209. (Fear conditioning, mice, Spain) Markram K et al. (2008) Abnormal fear conditioning and amygdala processing in an animal model of autism. Neuropsychopharmacology. 33(4):90-112. (Rats, Switzerland) Cordero MI et al. (2007) Stress amplifies memory for social hierarchy. Front. Neurosci. 1(1): 175-184 (rat, Switzerland) Lopez-Fernandez MA et al. (2007) Upregulation of Polysialylated Neural Cell Adhesion Molecule in the Dorsal Hippocampus after Contextual Fear Conditioning Is Involved in Long-Term Memory Formation. The Journal of Neuroscience. 27(17): 4552-4561. (Rats, France, Switzerland) Markram K et al. (2007) Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction. Neurobiology of learning and memory. 87(4): 573-582. (Rats, Switzerland) Poirier R et al. (2007) Paradoxical role of an Egr transcription factor family member, Egr2/Krox20, in learning and memory Frontiers in Behavioral Neuroscience 1(art 6): 1-12. (Mice, France) Toledo-Rodriguez M et al. (2007) Stress before puberty exerts a sex- and age-related impact on auditory and contextual fear conditioning in the rat. Neural Plast. In Press. (Rats, Switzerland) Markram K et al. (2006) Selective learning and memory impairments in mice deficient for polysialylated NCAM in adulthood. Neuroscience. 144(3): 788-796. (Mice, Switzerland)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention

STARTLE Software for Automated Startle Reflex Studies Related Hardware

➤ Combined Startle and Fear System, see pages 71 – 72

STARTLE software STARTLE is powerful and user-friendly software featuring a protocol editor. This allows the experimenter to build a wide variety of different protocols enabling the configuration of both standard (startle reflex habituation, prepulse inhibition of startle reflex, fear-potentiated startle reflex) and unusual user-defined protocols.

software species is hardware specific

Key Features

➤ Optimized animal movement detection for small animals! ➤ Versatile software allowing the configuration of a wide variety of protocols

➤ Sound frequency and amplitude controlled by software ➤ Synchronized running

➤ Provides a subject database as an alternative to manually managing subject information ➤ Provides traceable data for GPL compliance

➤ Records and stores the analog signals for further analysis ➤ No PCI cards required - has USB connection

The software can run up to 8 chambers simultaneously and in a synchronized manner. The software also provides standardized data (maximum amplitude and latency to maximum) in an automated manner. Two activity thresholds can also be set for an accurate user-controlled evaluation of additional such as duration, average or latency to the onset response. The run window shows the signal chart and corresponding raw data table online for every chamber. In each table, information about the status of the protocol is shown, together with the important parameters of the execution. Both signal chart and raw data table can be saved and reloaded for recalculating parameters using different activity thresholds. As required in the Good Practices of Laboratory (GPL) directives and instruction, STARTLE has been built in order to obtain traceable data: i.e. each session recorded can be linked to the corresponding experimental data (date, experimenter, animal data, protocol used, etc.).

Specifications Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM, 1 free USB for the protection key; 1 free RS-232 serial port for boxes connection (a USB-Serial adapter included in the software pack can be used when a RS-232 serial port is not available)

➤ Latency until the beginning of startle response

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

➤ Mean startle values for each trial type

System Requirements

Windows® XP (SP2 or Higher), Vista 32 – PC integrated standard sound card (DirectX compatible, RMS at least 0.5 Volts)

Parameters Measured

➤ Maximum amplitude of startle response

➤ Latency until the maximum amplitude of startle response ➤ Duration of startle response

➤ Average of the startle response

Components Included ➤ Software CD

➤ Cables and connectors ➤ Instruction manual

➤ Free software updates of the acquired system

Options

➤ Tailor-made experimental configuration setups upon request

Order # Model

Product

BH2 76-0284 STARTLE

Software to Control up to 8 Stations for Startle Reflex Studies

Citations Viosca J et al. (2009) Germline expression of H-RasG12V causes neurological deficits associated to Costello syndrome. Genes, Brain and Behavior. 8(1):60-71. (Startle, mouse, Spain) Ortiz-Abalia J et al. (2008) Targeting Dyrk1A with AAVshRNA attenuates motor alterations in TgDyrk1A, a mouse model of Down syndrome. Am. J. Hum. Genet. 83(4):479-88. (Startle, mouse, Spain)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Learning, Memory & Attention

FREEZING Software for Automated Fear Conditioning FREEZING Software FREEZING is a powerful and user-friendly tool for conducting fear conditioning experiments in rodents. The FREEZING protocol editor allows the experimenter to build a wide variety of protocols enabling the configuration of both standard (context-dependent fear conditioning, tone-dependent fear conditioning) and unusual user-defined protocols. The software can run up to 8 chambers simultaneously and in a synchronized manner. Two thresholds can be set for the detection of the animal freezing behavior: activity (for differentiating immobility from activity) and time (for eliminating any non-specific freezing episode which duration is lower than an user-defined duration). The run window shows the signal chart and corresponding raw data table online for every chamber. In each table, information about the status of the protocol is shown, together with the important parameters of the execution. Both signal chart and raw data table can be saved and reloaded for recalculating parameters using different activity and time thresholds. software species is hardware specific

Key Features

➤ Optimized animal movement detection for small animals ➤ Versatile software allowing the configuration of a wide variety of protocols

➤ Sound frequency and amplitude controlled by software ➤ Synchronized running

As required in the Good Practices of Laboratory (GPL) directives and instruction, FREEZING has been built in order to obtain traceable data: i.e. each session recorded can be linked to the corresponding experimental data (date, experimenter, animal data, protocol used, etc.).

Specifications Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM, 1 free USB for the protection key; 1 free RS-232 serial port for boxes connection (a USB-Serial adapter included in the software pack can be used when a RS-232 serial port is not available)

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

System Requirements

Windows® XP (SP2 or Higher), Vista 32 – PC integrated standard sound card (DirectX compatible, RMS at least 0.5 Volts)

➤ Provides a subject database as an alternative to manually managing subject information ➤ Provides traceable data for GPL compliance

➤ Records and stores the analog signals for further analysis ➤ No PCI cards required - has USB connection

Parameters Measured

➤ Onset time for each freezing event ➤ Duration of each freezing event

➤ Summary table for the total freezing in each state of the experiment

➤ Number and duration of freezing episodes in each user-defined interval of time

Components Included ➤ Software CD

➤ Cables and connectors ➤ Instruction manual

➤ Free software updates of the acquired system

Options

➤ Tailor-made experimental configuration setups upon request

Related Hardware

Order # Model

Product

BH2 76-0099 FREEZING

Software to Control up to 8 Stations for Fear Conditioning Studies

Citations Viosca J et al. (2009) Enhanced CREB-dependent gene expression increases the excitability of neurons in the basal amygdala and primes the consolidation of contextual and cued fear memory. Learn Mem. 16(3):198-209. (Fear conditioning, mice, Spain) Markram K et al. (2008) Abnormal fear conditioning and amygdala processing in an animal model of autism. Neuropsychopharmacology. 33(4):90-112. (Rats, Switzerland) Cordero MI et al. (2007) Stress amplifies memory for social hierarchy. Front. Neurosci. 1(1): 175-184 (rat, Switzerland) Lopez-Fernandez MA et al. (2007) Upregulation of Polysialylated Neural Cell Adhesion Molecule in the Dorsal Hippocampus after Contextual Fear Conditioning Is Involved in Long-Term Memory Formation. The Journal of Neuroscience. 27(17): 4552-4561. (Rats, France, Switzerland) Markram K et al. (2007) Amygdala upregulation of NCAM polysialylation induced by auditory fear conditioning is not required for memory formation, but plays a role in fear extinction. Neurobiology of learning and memory. 87(4): 573-582. (Rats, Switzerland)

➤ Combined Startle and Freezing System, see pages 71 – 72

74

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention Modular Operant Box for Operant Conditioning Modular Operant Behavior System

Key Features

➤ Entirely modular system

➤ Easily transformed between rat and mouse chamber ➤ Reduced number of cables

Modular Operant Box Our Modular Operant Chamber is an entirely modular experimental enclosure designed to conduct operant conditioning procedures (e.g. food reinforcement, DMTS, conflict tests, self-administration, etc).

➤ Up to 8 stations can be connected at once to PC through a single cable

The operant chamber is an entirely modular structure which allows complete disassembling or rearrangement to build a new space of different dimensions/components or to enable storage in the minimum space. It can be easily transformed from rat chamber to chamber (or vice versa).

Parameters Measured

A front door offers total accessibility inside the chamber. The mouse walls and cover can be of different material or color, since they are totally removable.

➤ Possibility of customization

➤ No PCI cards required - has USB connection, one cable links all! ➤ Number of responses (LE 85XCT)

➤ Number of reinforcements (LE 85XCT)

➤ Many user-defined parameters (PackWin software)

Components Included

➤ Operant Chamber (mouse or rat) ➤ Instruction manual

➤ Cables and connectors

Each chamber is associated with a Link Box which provides power to up to 8 (expandable to 16) Operant Modules (levers, lights, sound, dispensers, electrical shock) conferring to the chambers a full autonomy. Special accessories are provided for self-administration procedures. Only one cable connects the Link Box to the LE85XCT Programmer or PC (PackWin Software), this last for advanced protocol configuration and running.

➤ 2 year warranty

Options

➤ Link Box (power connection box for up to 8 modules) ➤ Wide range of modules ➤ Sound Attenuating Box

NOTE

For set-ups greater than 8 stations, please contact technical support for assistance.

➤ MPS push button

➤ Experiment programming unit (with ratio and interval schedules and shocker) ➤ PackWin software

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

75


Learning, Memory & Attention

Modular Operant Box for Operant Conditioning (continued) Specifications Base Dimensions

440 (W) x 360 (D) x 35 (H) mm

Working Area (Mouse)

200 (W) x 200 (D) x 250 (H) mm

Working Area (Rat)

250 (W) x 250 (D) x 250 (H) mm

Material Composition

Stainless steel, aluminum and methacrylate

Power Supply

110 V/220 V, 50/60Hz

Maximum Number of Stations (When Working with PC)

8 stations connected to a PC

Connection of Several Units to PC

No need of PC interfaces! Direct connection through one cable!

Certifications

CE compliant

Order # Model

Product

BH2 76-0146 LE1002CP

Operant Chamber Setup for Mice Including Pellets Dispenser, Lever, Light Stimuli, Mice Shock Grid and LINK BOX 01

BH2 76-0148 LE1005CP

Operant Chamber Setup for Rats Includes Pellets Dispenser, Lever, Light Stimuli, Rat Shock Grid and LINK BOX 01

BH2 76-0147 LE1002CL

Operant Chamber Setup for Mice Includes Drop Liquid Dispenser, Lever, Light Stimuli, Mice Shock Grid and LINK BOX 01

BH2 76-0149 LE1005CL

Operant Chamber Setup for Rats Includes Drop Liquid Dispenser, Lever, Light Stimuli, Rat Shock Grid and LINK BOX 01

STANDARD, PRECONFIGURED OPTIONS

Citations Hayat Harati M et al. (2009) Attention and memory in aged rats: impact of lifelong environmental enrichment. Neurobiology of aging. In Press. (5CSRT, rat, France) Hernandez-Rabaza V et al. (2009) Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal. Neuroscience. 159(1):59-68. (NMTP procedures, rat, Spain) Augustin-Pavon C et al (2008) Sex versus sweet: Opposite effects of opioid drugs on the reward of sucrose and sexual pheromones. Behav. Neurosci. 122(2): 416-425. (sucrose preference, mice, Spain) Hernández-Rabaza et al. (2008) The hippocampal dentate gyrus is essential for generating contextual memories of fear and drug-induced reward. Neurobiology of Learning and Memory, 90(3):553-559. (Fear conditioning, rat, Spain) Pellon R et al. (2007) Pharmacological analysis of the effects of benzodiazepines on punished schedule-induced polydipsia in rats. Behav. Pharmacol. 18(1): 81-87. (Punished schedule-induced drinking, rats, Spain) Pérez-Padilla A, Pellón R (2006) Level of response supresión and amphetamine effects on negatively punished adjunctive licking. Behav. Pharmacol. 17(1): 43-49. (Punished schedule-induced drinking, rats, Spain) Conejo NM et al. (2005) Brain metabolism after extended training in fear conditioning task. Psicothema. 17(4): 563-568 (disruption of lever pressing in fear conditioning task, Rat, Spain) Manrique T et al. (2005) Early learning failure impairs adult learning in rats. Dev. Pshychobiol. 46(4): 340-349. (Rat, Spain). Toro JM et al. (2005) Backward Speech and Speaker Variability in Language Discrimination by Rats. J. Exp. Psychol. 31(1): 95–100. (rat, Spain) Lopez-Moreno JA et al. (2004) Long-lasting increase of alcohol relapse by the cannabinoid receptor agonist WIN 55,212-2 during alcohol deprivation. J. Neurosci. 24(38): 8245-8252. (ethanol selfadministration, rat, spain) Pérez-Padilla A, Pellón R (2003) Amphetamine increases schedule-induced drinking reduced by negative punishment procedures. Psychopharmacol. 167(2): 123-129. (Punished schedule-induced drinking, rats, Spain) Burgal M et al. (1988) Asymmetric incorporation of [14C]cyanate and of fluorescein isothiocyanate in mamillary body of conditioned rats. Neurochem. Res. 13(5): 435-442. (learning, Rat) Cuomo V et al. (1983) Behavioral and biochemical effects in the adult rat after prolonged postnatal administration of haloperidol. Psychopharmacol. 81(3): 239-243. (Differential reinforcement of low rate schedule, rat, Italy) Cuomo V et al. (1981) Enduring behavioral and biochemical effects in the adult rat after prolonged postnatal administration of haloperidol. Psychopharmacol. 74(2): 166-169. (Differential reinforcement of low rate schedule, rat, Italy)

Contact Technical Support for the Broad List of Additional Modules for our Modular Operant Chambers! To customize your own system, select options below: OPTIONS

76

BH2 76-0151 LE1002

Modular Mice Operant Chamber

BH2 76-0152 LE1005

Modular Rats Operant Chamber

BH2 76-0153 LE100201

Mice Shockable Grid

BH2 76-0154 LE100501

Rats Shockable Grid

BH2 76-0155 LE1050

MPS Push Button for LE85XCT

BH2 76-0156 LINKBOX01

Link & Power for up to 8 Modules

BH2 76-0157 LE26

Sound Attenuating Box

BH2 76-0158 LE85XCT

PROGRAMMER with Ratio & Interval Schedules and Shocker

BH2 76-0159 LE10026

Shock Generator with Scrambler, 0 - 2 mA Output

BH2 76-0002 PACKWIN

PC software to Control up to 8 Operant Chambers

BH2 76-0160 LE1010

Harness Set for Electrical Stimulation

BH2 76-0161 LE12605

Electrical Stimulator

BH2 70-2208 –

Pump 11 Plus

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention PackWin Software

Packwin System

PackWin Software PackWin is a user-friendly and versatile software developed for the Windows platform. This software offers a powerful, yet straightforward, tool for developing an unmatched range of experiments in different types of behavior chambers; typically those for operant conditioning, self-administration and procedures using the nine-hole box. The user-interface of PackWin has been recently re-designed, providing even greater flexibility and simplicity, turning the system into an attractive tool for both experienced and for non experienced users. This software does not require previous knowledge in programming!

software species is hardware specific

Parameters Measured

➤ Number of response (nose-spoke, lever pressing etc.) for the whole session or by user-defined interval of time ➤ Latency of response

➤ Number of reinforcement given (food, drug, drink, shock etc.) ➤ Number of trials made

➤ Total duration of the experiment ➤ Cumulated curve graphs ➤ Response pattern graphs

➤ Built-in 5/9 hole experiments report (number of correct, incorrect, premature, anticipated responses and omission, choice accuracy etc.)

Key Features

➤ NEW simplified user-interface

➤ NEW time-saving batch analysis and built-in reports

➤ NEW Includes our unique new Virtual Box, a specific box test panel and simulator ➤ Combines sophistication with straightforwardness

➤ Maximal flexibility provided without requiring any specific knowledge in programming ➤ Cumulated and response pattern graphs ➤ Simplified communications to hardware ➤ Subject Data Base ➤ Result traceability

Components Included

The different options of the PackWin protocol editor allow the user to build a wide variety of different protocols. It enables the configuration of basic programs for operant procedure (fixed and variable ratio, fixed or variable interval, fixed or variable DRL, positive and negative reinforcement, extinction, probability to obtain a reinforcement, etc.) with or without discriminative stimuli (light, sound) as well as more specific and complex user-defined protocols (conflict, DMTS, 5 choice serial reaction task etc.). New assistant panels are now available for the configuration of 5-choice serial reaction task procedures! The software can run up to 32 chambers depending on the characteristics of the associated chamber. In addition, each chamber can run independently from the rest of the selected chambers or in a synchronized manner. Desired protocols can be selected separately for each chamber. The registered sessions can be re-analyzed for generating all the reports and graphs typically needed when conducting operant behavior studies (summary data report with 1 row by subject, response by time report, historic events report, cumulated curve graph, response pattern plot). Individual and batch analyses are facilitated in a new advanced analysis panel in which the user can process the registered sessions using different time settings (full session, userdefined start and stop time, session split in different interval time of analysis). Raw data tables can be stored in Excel format for further analysis. All graphs are directly exportable to image format and associated raw data to XLS format. Unique to only our system! PackWin now provides the option of running experiment with virtual boxes! This new enhancement allows the user to configure and verify the protocols created anywhere without requiring direct connection with the real boxes. This new feature is also perfect for teaching purposes! As required in the Good Practices of Laboratory (GPL) directives and instruction, PackWin has been built in order to obtain traceable data: i.e. each session recorded can be linked to the corresponding experimental data (date, experimenter, animal data, protocol used, etc.).

➤ Software installation CD ➤ Cables and connectors ➤ Instruction manual

➤ Free software updates of the acquired system

Options

➤ Tailor-made Experimental Configuration Setups upon request * Contact us for more information about set-ups larger than 8 stations.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

77


Learning, Memory & Attention PackWin Software (continued) Related Hardware

➤ Modular Operant Box, see pages 75 – 76 ➤ Vogel Test, see page 93

➤ 5/9 Hole Box, see page 79

➤ Self Administration Box, see page 101

Specifications Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM, 1 free USB for the protection key; 1 free RS-232 serial port for boxes connection (a USB-Serial adapter included in the software pack can be used when a RS-232 serial port is not available)

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

System Requirements

Windows® XP (SP2 or Higher), Vista 32

Order # Model

Product

BH2 76-0002 PACKWIN

PC Software to Control up to 8 Experimental Chambers

Citation Hayat Harati M et al. (2009) Attention and memory in aged rats: impact of lifelong environmental enrichment. Neurobiology of aging. In Press. (5CSRT, rat, France) Hernandez-Rabaza V et al. (2009) Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal. Neuroscience. 159(1):59-68. (NMTP procedures, rat, Spain) Augustin-Pavon C et al (2008) Sex versus sweet: Opposite effects of opioid drugs on the reward of sucrose and sexual pheromones. Behav. Neurosci. 122(2): 416-425. (sucrose preference, mice, Spain)

78

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention

5/9 Holes for Attention Performance 5/9 Holes Box

The nine-hole box is assembled with black aluminum walls and a transparent front door. The box is equipped with an arc of 9 contiguous apertures set into the rear wall, a house light, a food pellet dispenser and a ‘pusher’ to detect the nose-pokes into the food holder. The holes not used in the experiment may be blocked up using a metal insert. Each hole is equipped with photocell beams and internal LED providing visual cues specific to each hole. The intensity of the LED can be adjusted in Link Box using the digital selector. The box is placed on a stainless-steel platform and the associated tray is easily removable to clean. Panlab/Harvard Apparatus also offers an optimized nine-holes box for performing test in mice. This new box is supplied with 9 pellet dispensers in order to give the reward directly into the right stimulus hole when a correct response is fulfilled.

➤ Associated with a very complete and flexible software - PackWin

All Panlab/Harvard Apparatus nine-hole boxes are associated with the potent and versatile PackWin software in order to control the experiment (protocol configuration, experiment running) and obtain relevant data such as correct responses, incorrect responses, omissions, prematureresponses, perseverant responses, time out responses, total receptacle head entries, etc.

➤ Neither PC interface nor PC cards are required

Different experimental paradigms for sustained attention, animal models of impulsive behavior and lateralized-discrimination task can be conducted using the nine-hole box.

Key Features

➤ Hole LEDs with adjustable intensity

➤ Up to 8 stations can be connected at once to PC through a single cable

Parameters Measured

➤ Number of correct responses

➤ Number of incorrect responses

➤ Number of persevering actions ➤ Number of omissions

➤ Number of anticipatory responses ➤ Number of trials performed ➤ Responses latency

➤ Reinforcement (food, drink) intake latency ➤ Number of responses during the time-out ➤ And many user-defined parameters

Components Included

As an example, in the 5-choice serial reaction time task, short-lasting stimuli are given in pseudo-randomized order in one of the holes of the cage (commonly, hole 1, 3, 5, 7 or 9). If the animal nose-pokes into the correct hole, a reinforcement (pellet) is given. If the animal nose-pokes into an incorrect hole, a time-out period (no light) is given and next trial begins. The choice accuracy (% of correct responses) gives an idea of the functional integrity of the attention as well as learning processes. These parameters are mostly altered in animal models of Schizophrenia and Alzheimer Diseases.

Specifications Cage Dimensions:

➤ Nine holes box (with 9 stainless steel lids)

LE509 Rat Cage

252 (W) x 280 (D) x 240 (H) mm internal; 440 x 360 x 315 mm external

➤ Pellets dispenser

LE507 Mouse Cage

190 (W) x 220 (D) x 240 (H) mm internal; 440 x 360 x 315 mm external

➤ Control unit with RS-232 communication port ➤ Feeder with light-beam detection technology ➤ Stimuli light

➤ Cables and connectors

Holes Dimensions: Rat

23mm hole diameter; 14mm hole deep

Mouse

13mm hole diameter; 10mm hole deep

➤ Instruction manual

Material Composition

Plexiglass, aluminum, stainless steel

➤ 2 year warranty

Maximum Number of Stations

8 stations connected to a PC

Power Supply

110 V/220 V, 50/60Hz

Certifications

CE compliant

Order # Model

Product

BH2 76-0000 LE509

Rats 5/9 Holes Cage w/PC Interface

BH2 76-0001 LE507

Mice 5/9 Holes Cage w/PC Interface

BH2 76-0002 PACKWIN

PC Software to Control up to 8 Cages

BH2 76-0367 LE512

Mice 9 Hole Box w/Pellet Dispenser

➤ Set of spare fuses

Options

➤ PackWin software to control up to 8 boxes simultaneously

5/9 Holes The nine-hole box is commonly used to evaluate attention performance using a visual discrimination task in laboratory animals. The nine-hole box is composed of a test chamber, food or drink dispenser, a Link Box to connect it to the PC and the PackWin software.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Learning, Memory & Attention

Passive Avoidance Box to Assess Working Memory Passive Avoidance Box

Key Features

Passive Avoidance Box

➤ Very precise and stable intensity of shock delivered into the black compartment

Passive Avoidance is fear-motivated tests classically used to assess short-term or long-term memory on small laboratory animals.

➤ Weight transducer technology for accurate animal detection ➤ Neither PC interface nor PC cards are required

➤ Safety system which guarantees that the shock intensity received by the animal is always the same value independently of the grid bars treaded

Parameters Measured

➤ Latency to enter into the black compartment

Components Included ➤ Passive Avoidance Box

➤ Control unit with RS-232 communication port

➤ Motorized door (to be controlled either by LE2708 or ShutAvoid software) ➤ SeDaCom software

➤ Cables and connectors ➤ Instruction manual ➤ 2 year warranty

Options

Passive Avoidance working protocols involve timing of transitions, i.e. time that the animal takes to move from the white compartment to the black one after a conditioning session. During the conditioning session, entry into the black compartment is punished with a mild inescapable electrical shock. Our Passive Avoidance box (LE870/872) is defined by a large white illuminated compartment and a small black dark compartment separated by a guillotine gate. The animal’s position is detected by using high sensitivity weight transducers providing greater accuracy and reliable detection (zones entries) systems utlizing on photocell beams or on grid floor displacements. Panlab/Harvard Apparatus Passive Avoidance boxes may be controlled either through LE2708 Programmer or ShutAvoid software. The first option is recommended for one single box set-ups, and may be combined with the included SeDaCom software. SeDaCom enables data transfer from the programmer to a PC through a RS-232 port. The connection is direct between programmer to a PC. No PCI card is needed! The link is carried out by one only cable from one Box to the other. The first box is connected to PC or Laptop by the RS-232 port or USB. The second option is suitable for controlling a number of boxes simultaneously.

➤ LE2708 Avoidance Programmer including shocker

➤ ShutAvoid software to control up to 8 Active or Passive boxes ➤ LE10026 Shocker unit with scrambler (0-2mA output)

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Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Learning, Memory & Attention

Passive Avoidance Box to Assess Working Memory Specifications Mouse Box Dimensions

250 (W) x 250 (D) x 240 (H) mm white compartment; 195 x 108 x 120 mm black compartment

Rat Box Dimensions

310 (W) x 310 (D) x 240 (H) mm white compartment; 195 x 108 x 120 mm black compartment

Minimum Weight Detected

10 grams (mouse box); 40 grams (rat box)

Material Composition

Methacrylate, aluminum, stainless steel

Computer Requirements

PC (Windows® 95, 98, ME, NT, 2000 and Vista) (with SeDaCom)

Maximum Number of Stations

8 stations connected to a PC

Connection of Several Units to PC

Neither PC interface nor PC card are required. One cable connects all units to the PC

Certifications

CE compliant

Power Supply

110 V/220 V, 50/60Hz

Order # Model

Product

BH2 76-0199 LE870

Passive Avoidance Cage, Rats

BH2 76-0200 LE872

Passive Avoidance Cage, Mice

BH2 76-0201 LE2708

Avoidance Programmer with Shocker Unit Included

OPTIONS

BH2 76-0202 SHUTAVOID

Software to Control up to 8 Active/Passive Boxes

BH2 76-0159 LE10026

Shock Generator with, Scrambler, 0-2 mA Output

Citations Cuhna C et al. (2009) Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments. Neurobiology Disease. 33(3):358-368. (mouse, Italy) Monleon S et al. (2009) Effects of oxotremorine and physostigmine on the inhibitory avoidance impairment produced by amitriptyline in male and female mice. Behav. Brain Res. (mouse, Spain) In press. Martín-García E et al. (2008) Neonatal finasteride induces anxiogenic-like profile and deteriorates passive avoidance in adulthood after intrahippocampal neurosteroid administration. Neurosci. 154(4):1497-1505. (rat, Spain) Rueda N et al (2008) Effects of chronic administration of SGS-111 during adulthood and during the preand post-natal periods on the cognitive deficits of Ts65Dn mice, a model of Down síndrome. Behav. Brain Res. 188(2):355-367 (Mouse, Spain) Tramullas M et al (2008) Facilitation of avoidance behaviour in mice chronically treated with heroin or methadone. Res. Rep. 189(2):332-340 (Mouse, Spain) Bouet V et al. (2007) Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse. Exp. Neurol. 203(2):555-567 (Mouse, France) Haelewyn B et al. (2007) Long-term evaluation of sensorimotor and mnesic behaviour following striatal NMDA-induced unilateral excitotoxic lesion in the mouse. Behav. Brain Res. 178(2):245-243 (Mouse, France)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Anxiety Guide

Anxiety is the most common and most studies psychiatric field in humans. Anxiety is characteristic of situations that pose either real or imaginary threats to the organism and then includes changes in behavior. In theory, anxiety is an adaptive emotion that permits, by developing behavioral and physiological changes, to appropriately react to a stressful situation in order to resolve it (by escaping, fighting…). However, pathological variants of anxiety can occur and be deleterious for those affected. Anxiety disorders are reported as the most prevalent of the psychiatric diseases.

Anxiety disorders were only recognized in 1980 by the American Psychiatric Association. Before this recognition, people experiencing one of these disorders usually received a generic diagnosis of “stress” or “nerves”. Due to the lack of understanding these disorders, very few received the necessary treatment. Since 1980, international research has shown the severe disabilities associated with these disorders. Most of these disabilities can be prevented with eary diagnosis and effective treatment. At the present time, benzodiazepines are the most common drug prescribed for relieving anxiety symptoms due to their action on the central nervous system via the modulation of the GABAA receptors. These substances were basically discovered by chance by Sternbach, working for Hoffman La Roche in New Jersey in 1957. The original compound was found to have hypnotic, anxiolytic and muscle relaxant effects and the first benzodiazepine, chlordiazepoxide (Librium) was launched in the UK in 1960, followed by diazepam (Valium) in 1963. By 1983, there were 17 benzodiazepines on the market worth nearly $3 billion worldwide. There are now 29 benzodiazepines available in the US and Europe for a variety of clinical uses.

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However, as the use of benzodiazepines is thought to provoke undesired effects such as physical dependence, research laboratory and pharmaceutical industry still focus their effort in understanding better the genetic and neurobiological substrates of anxiety and in screening new chemicals for their putative therapeutic effects. In this context, rodent behavioral models of anxiety have been developed and constitute an excellent tool for these purposes. Anxiety in rodents is comparable and analogous to anxiety in humans in terms of behavioral and peripheral manifestations an dhas been shown to share physiological mechanisms. The methods to assess anxiety-related behaviors in laboratory rodents are commonly divided in two categories: unconditioned (ethological) and conditioned (learned) tests. Unconditioned test are usually based on conflicts between exploratory approach/avoidance natural tendencies. Conditioned tests are based on the change of responses controlled by conditioning procedures.


Anxiety Guide Behavioral Test

Behavioral Test

Open Field Test

Elevated Plus Maze

The open field test is classically used to assess anxiety in rodents. This test is based on conflicting innate tendencies of avoidance of bright light and open spaces (that ethologically mimic a situation of predator risk) and of exploring novel environment. When placed into a brightly lit open field for the first time, rats and mice tend to remain in the periphery of the apparatus or against the walls (thigmotaxis). It had been shown that anxiolytics administration increases exploration time in the center of the open field while stressful stimuli decrease the number of center visits. Open field activity, therefore, represents a valid measure of marked changes in “anxietylike” behaviors in drug-treated and genetically manipulated animals. Open-field procedure

Reasons for Choosing This Test ➤ Exploration based conflict task ∑ Based on innate behavioral tendencies (ethological test) ∑ Central area versus periphery choice ∑ Simple to setup and use ∑ Short-lasting experiment ∑ Standard test for anxiety widely referenced in behavioral literature ∑ Sensitive for both rats and mice

The Elevated Plus Maze is a widely used animal model of anxiety that is based on two conflicting innate tendencies: exploring a novel environment and avoiding elevated and open spaces constituting situations of predator risk. The apparatus consists of two open (stressful) and two enclosed (protecting) elevated arms that form a “plus” or cross. Time spent in exploring enclosed versus open arms indicates that the anxiety level of the animal. When placed into this apparatus, naïve mice and rats will, by nature, tend to explore the open arms less due to their natural fear of heights and open spaces. IN this context, anxiolytics generally increase the time spent exploring the open arms and anxiogenics have opposite effect, increasing the time spent into the closed arms.

Reasons for Choosing This Test ➤ Exploration based conflict task ∑ Based on innate behavioral tendencies (ethological test) ∑ Open elevated arm versus closed arm choice ∑ Simple to setup and use ∑ Short-lasting experiment

Reasons for Not Choosing This Test ➤ Repeated exposition induces habituation ∑ Influenced by a host of variables ∑ Needs intact locomotor performances

Reasons for Not Choosing This Test ➤ Repeated exposition induces habituation ∑ Influenced by a host of variables ∑ Needs intact locomotor performances ∑ Difficult to dissociate impaired locomotor activity from anxiety induced suppression of exploration

Related Human Disease/Applications ➤ Anxiety ∑ Drug screening ∑ Phenotyping

Related Human Disease/Applications ➤ Anxiety ∑ Drug screening ∑ Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Anxiety Guide Behavioral Test

Behavioral Test

Black and White Boxes

Aron Test

The Black and White test, also known as the light-dark test, is based on the conflict of natural tendencies of rodents to avoid lighted and open areas and to explore novel environments. The apparatus contains a white opened compartment and a small enclosed black compartment. Relative time spent in exploring each compartment indicates the anxiety level of the animal: avoidance to the brightly lit area is considered reflecting “anxiety-like” behavior. When treated with anxiolytic drugs, rodents spend more time in this area, an effect observed due to a decrease in anxiety.

The Aron Test, also known as the Four Plate Test, allows a quick characterization of putative anxiolytic compounds in naïve animals. The test consists basically of setting animals into a square chamber, the floor of with was composed of four metal plates, and monitoring their locomotor behavior by counting the number of crossings from one plate to another. Exploration of the chamber was markedly suppressed in response in subjects that received electrical shock at each crossing compared to control animals that are not shocked during their exploration.

Reasons for Choosing This Test ➤ Exploration based conflict tasks ➤ Based on innate behavioral tendencies (ethological test) ➤ Light versus dark compartment choice ➤ Standard test for anxiety widely referenced in behavioral literature ➤ Simple to setup and use ➤ Short-lasting experiments ➤ Sensitive for both rats and mice

Reasons for Choosing This Test ➤ ➤ ➤ ➤

Punishment based conflict test No need for food or drink deprivation Short-lasting experiments Sensitive for both rats and mice

Reasons for Not Choosing This Test ➤ Involves aversive/stressful stimulus (foot shock) ➤ Influenced by non-specific changes in cognition and nociception

Reasons for Not Choosing This Test

Related Human Disease/Applications

➤ ➤ ➤ ➤

➤ Anxiety ➤ Drug Screening ➤ Phenotyping

Repeated exposition induces habituation Influenced by a host of variables Needs intact locomotor performances Difficult to dissociate impaired locomotor activity from anxiety-induced suppression of exploration

Related Human Disease/Applications ➤ Anxiety ➤ Drug screening ➤ Phenotyping

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Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Anxiety Guide Behavioral Test

Vogel Test The Vogel Test paradigm is a popular conflict model in which water deprived rats and mice first learn to lick from a water spount in an operant chamber. Then, usually after a period of unpublished licking, responses are punished with mild footshocks, including a significant reduction of drinking. In this context, administration of anxiolytics of shown to inhibit shock reduction of drinking. In this context, administration of anxiolytics is shown to inhibity shock-induced drinking suppression.

Reasons for Choosing This Test ➤ Punishment based conflict test

Reasons for Not Choosing This Test ➤ ➤ ➤ ➤

Classically used in rat, underemployed in mice Needs food or drink deprivation Involves aversive/stressful stimulus (footshock) Influenced by non-specific changes in response rate, cognition, basal water/food intake and nociception

Related Human Disease/Applications ➤ Anxiety ➤ Drug screening

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Depression Guide

The term “depression” is commonly used to reflect a variety of experiences ranging from normal, transient unhappiness to pathological states of hopelessness, as defined in the DSM-IV (for diagnostic and Statistical Manual of Mental Disorders, 4th Edition). Owing to its common psychological and social etiologies, depression is hard to model in non-human subjects, but few experimental tests have been developed to display “depressive-like” symptoms in rodents. Depression, characterized by disturbances in mood, sleep, appetite, energy, motivation, hedonic capacity and thinking is among the most prevalent forms of mental illness. The major theory of depression, the monoamine hypothesis, proposes that decreasing the levels of one or more brain monoamine neurotransmitters, such as 5hydroxytryptamine (serotonin) (5-HT), noradrenalin or dopamine, can be responsible of depressive symptoms, In this way, antidepressant drugs mainly act on serotoninergic and noradrenergic pathways in the brain.

Since research in humans is limited, animal models of depression have been developed, whereas many symptoms of depression cannot be easily measured in laboratory rodents (e.g. depressed mood, feelings of worthlessness, suicide tendency). However, some behavioral tests have been shown to be very effective in evaluating depressive symptoms and are classically used to predict the antidepressant effect of new medications. They also provide potentially useful models in which to study neurobiological and genetic mechanisms underlying depressive behavioral changes. These paradigms have strong predictive validity and behavioral responses are reliable and robust within and across laboratories.

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The existence of numerous behavioral tests to measure depression in rodents reflects the heterogeneity of depressive-like symptoms. In this way, forced swimming test and tail suspension test are classical paradigms used to evaluate behavioral despair. Hopelessness, reported as a common trait of depression in humans, is mimicked in rodents by the paradigm of learned helplessness. Finally, anhedonia is classically reflected by a decrease of sweet solution consumption by depressive rodents.


Depression Guide Behavioral Test

Behavioral Test

Rota Rod Test

Grip Strength Test

One relatively simplistic and widely used model of depression is the forced-swimming paradigm originally adopted by Porsolt et al (1978). Naïve rats and mice forced to swim in an aversive and confined environment innately fight to escape the apparatus. Following failed attempts to escape, they become immobile (i.e. float), a behavior generally considered as despair, “depressive-like” behavior. Prior treatment with antidepressants decrease the time spent immobile and increases the latency to reach the first immobility episode.

The tail suspension test was developed as an alternative to the Forced Swimming Test, yet the concept remains the same. Rodents, suspended by their tail, innately attempt to escape from this aversive situation. However, following failed attempts to escape, they experience despair and become immobile. The magnitude of immobility is considered to be correlated with the depressive state of the subjects and is significantly decreased by antidepressants.

Reasons for Choosing This Test ➤ Despair model ➤ High predictability for antidepressant effects in humans ➤ Based on innate behaviors ➤ Sensitive for both mice and rats ➤ Widely used in literature ➤ Simple to setup and use ➤ Short duration experiment ➤ Can be automated (measurement subjectivity)

Reasons for Not Choosing This Test ➤ Repeated exposure induces habituation ➤ Influenced by non-specific changes in motor performances

Related Human Disease/Applications ➤ Depression ➤ Drug Screening ➤ Phenotyping

Reasons for Choosing This Test ➤ Despair model ➤ High predictability for antidepressant effects in humans ➤ Based on innate behaviors ➤ Widely used in literature ➤ Simple to setup and use ➤ Short duration experiment ➤ Can be automated (measurement subjectivity)

Reasons for Not Choosing This Test ➤ ➤ ➤ ➤ ➤

Repeated exposition induces habituation Can only be assessed in mice Difficult with some mice strains (C57BL/6) Repeated exposure induces habituation Influenced by non-specific changes in motor performances

Related Human Disease/Applications ➤ Depression ➤ Drug Screening ➤ Basal Depressive-like state Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Anxiety & Depression Elevated Plus Maze Elevated Plus Maze

The Panlab/Harvard Apparatus elevated-plus-maze is currently built in two different configurations (each one available for mice or rat): •

Basic maze which can be associated to our SMART or Smart JUNIOR Video-Tracking System

Maze equipped with rows of infrared photocells connected to a computer through the LE3846 control unit and the Panlab/Harvard Apparatus MAZESOFT-4 software.

Specifications Dimensions

Key Features

➤ Modular structure which allows storage in minimum space ➤ Available in a number of colors

Parameters Measured

➤ Animal position and number of entries into the different sectors (see MAZESOFT-4) ➤ Animal position, speed, distance and more (see SMART or Smart JUNIOR video-tracking)

Components Included ➤ Gray walls ➤ PlusMaze

➤ MAZESOFT-4 Software and LE3846 Interface for PC (only for LE846 and LE848) ➤ 2 year warranty

Options

➤ SMART or Smart JUNIOR Video Tracking System (only for LE840 and LE842)

Elevated Plus Maze The standard Elevated Plus Maze is commonly used to assess anxietylike behavior in laboratory animals. The maze is usually a cross shaped maze with two open arms and two closed arms, which is elevated above the floor. This task exploits the conflict between the innate fear that rodents have of open areas versus their desire to explore novel environments. Security is provided by the closed arms whereas the open arms offer exploratory value. When anxious, the natural tendency of rodents is to prefer enclosed dark spaces to opened brightly lit spaces. In this context, anxiety-related behavior is measured by the degree to which the rodent avoids the unenclosed arms of the maze.

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LE840/846 Rats Maze

1000 (W) x 1000 (D) x 500 (H) mm grey color walls; arms: 100 (W) x 450 (D) mm black color arms.

LE842 Mice Maze

650 (W) x 650 (D) x 150 (H) mm grey color walls; arms: 60 (W) x 295 (D) mm black arms

LE848 Photoelectrical Cells Mice Maze

640 (W) x 640 (D) x 550 (H) mm, arms: 60 (W) x 295 (D) mm for normal mice; 370 (W) x 370 (D) x 550 (H) mm, Arms: 60 (W) x 160 (D) mm for very small mice (provided with 2 interchangeable arm dimensions)

Material Composition

Methacrylate, aluminum

Transparent Walls Height

100 mm rats

Position Detection Technique

IR beams with MAZESOFT-8 or video-tracking system

Power Supply (When Applicable)

110 V/220 V, 50/60Hz

Certifications

CE compliant

Order # Model Product BH2 76-0074 LE840

Rats Elevated Plus Maze

BH2 76-0075 LE842

Mice Elevated Plus Maze

BH2 76-0076 LE846

Rats Elevated Plus Maze with Position Detection and MAZESOFT-4 Software Include

BH2 76-0077 LE848

Mice Elevated Plus Maze with Position Detection and MAZESOFT-4 Software Included

BH2 76-0078 LE843

T Maze Variant for Mice

BH2 76-0079 LE847

Y Maze Variant for Mice

BH2 76-0028 SMART

Advanced Video-Tracking Software for LE840/842 Standard Maze

BH2 76-0029 SMART JUNIOR

Standard Video-Tracking Software for LE840/LE842

BH2 76-0486 LE841

Transparent wall option for Ethological studies only for LE840

OPTIONS

Citations Lalonde and Strazielle (2008) Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice. J. Neurosci. Meth. 171(1):48-52 (mouse, Canada) Lalonde et al (2008) Effects of a B-vitamin-deficient diet on exploratory activity, motor coordination, and spatial learning in young adult Balb/c mice. Brain Res. 1188:1122-131 (mouse, Canada) Lalonde and Qian (2007) Exploratory activity, motor coordination, and spatial learning in Mchr1 knockout mice. Behav. Brain Res. 178(2):293-304 (mouse, Canada) Balerio GN, Aso E, Maldonado R. (2005) Involvement of the opioid system in the effects induced by nicotine on anxiety-like behavior in mice. Psychopharmacol. (Berl) in press. Yau JLW et al. (2002) Chronic treatment with the antidepressant amitriptyline prevents impairments in water maze learning in aging rats. J. Neurosci. 22(4): 1435-1442. (standard maze, rat, UK)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Anxiety & Depression

MAZESOFT-4 Software for Automated Elevated-Plus Maze Related Hardware

➤ Elevated Plus Maze, see page 88

MAZESOFT-4 Software MAZESOFT-4 is an easy and complete software for monitoring ElevatedPlus Maze experiments. It has been specially designed to work with the Panlab/Harvard Apparatus Plus Maze equipped with rows of infrared photocells for the automated detection of animal position. MAZESOFT-4 is easy to configure as the user only has to enter the desired duration of experiment. A “trial header” can be use for recording all the necessary information associated with the current experiment (code of trial, experimenter, challenge, dose, subject identification, comments). software species is hardware specific

Key Features

➤ Complete and easy-to-use for standard experiments

➤ Use of photo cell technology for animal position detection ➤ Provides integrated parameters (ie: permanence time in arms, number of entries)

➤ Data reports can be re-organized according to factors entered in the trial header (ie: animal, groups)

Parameters Measured

➤ Number of visits into the zones (or association of zones) ➤ % of visits into the zones / total number of visits

➤ Total permanence time in each zone (or association of zones)

The Plus Maze is divided into 9 sections: 4 identified arms (2 open and 2 closed), each one divided into proximal and distal section and a central area. One experiment can be composed of several trials, depending on the number of experimental groups and animals per group used in the study. During each trial, the elapsed time, permanence time in each area and current position of the animal can be visualized in real-time. Full information about the animal’s position is also shown graphically on the screen. MAZESOFT-4 provides two types of result presentations: a raw data table and integrated results. The raw data table initiates with the header of the trial (name of the experimenter, code identifications, etc.) and continues with the detailed chronological listing of the animal positions for each trial. Integrated results calculated from the raw data table are provided in an additional summary table. For each arm, the information is separately given for the proximal zone, for the distal zone and for both of the zones of the arm. Identical information is shown for the base zone in the middle of the maze and for the union for opposite arms (closed and open arms).

➤ % of permanence time in each zone / total duration of the trial

The tables of trials can be re-organized before exportation according to parameters previously entered in the trial header (by subjects, by groups, by experimenter, etc.).

➤ % of the mean time of visit duration into each zone / total duration of the trial

Data from the raw data base and from the table of result can be easily exported in formats widely used to perform complementary analysis (Word, Text, HTML or Excel).

➤ Mean time of visit duration into each zone (or association of zones)

➤ Number of entries into each zones (or association of zones) ➤ % of the entries into each zone / total number of entries ➤ Chronological sequence of animal displacements

Components Included

➤ Software and USB protection key ➤ PCI-7200

➤ Cables and connectors

This MAZESOFT-4 Software in not available as a separate product. It is included with the following systems, BH2 76-0076 Rats Elevated Plus Maze with Position Detection and BH2 76-0077 Mice Elevated Plus Maze with Position Detection. see page 88 for complete descriptions.

Specifications Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM with PCI 32-bit bus master expansion slot available and 1 free USB for the protection key

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

System Requirements

Windows® XP (SP2 or Higher), Vista 32

➤ Instruction manual

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Anxiety & Depression Open Field Box Open-Field Boxes

Parameter Measured

Video Tracking System Suggested

➤ Optimized design for videotracking purpose

Locomotor Activity

SMART & Smart JUNIOR

Rearing

SMART

➤ Easy to clean

Permanence Time and Entries Into the Center

SMART & Smart JUNIOR

Permanence Time and Entries Close to the Walls

SMART & Smart JUNIOR

Key Features

➤ Material non-odor absorbent

Open Field Boxes Open Field experiments allow the evaluation of animal basal activity and its evolution, in response to novelty or anxiogenic environment, to pharmacological treatment, lesion or genetic modification. Panlab/Harvard Apparatus proposes square openfields available for rats and mice. The arena is made of durable material which has the advantage to be non-odor absorbent and easy to clean. The arena is surrounded by high walls and is available in different non reflective colors for videotracking purposes. The system is entirely collapsable for enabling storage in the minimum space. The floor can be divided into equal squares under request for the direct counting of animal activity. Possibility of customization, contact Technical Support for more details!

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Order # Model

Product

BH2 76-0189 LE800S

Square Open-Field Box for Rat: 900 (W) x 900 (D) x 400 (H)mm, Grey

BH2 76-0190 LE802S

Square Open-Field Box for Mouse: 450 (W) x 450 (D) x 400 (H) mm, Grey

BH2 76-0439 LE800SC

Open Field Divider for 4 Rats for use with LE800S

BH2 76-0401 LE802SC

Open Field Divider for 4 Mice for use with LE802S

Round Open-Field Boxes available by special order. Please contact our technical support staff for more information.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Anxiety & Depression

Aron Test for Screen Anxiolytic Substances Aron Test Box

Specifications Cage Materials

White, transparent plastic and stainless steel

Dimensions

18 x 25 x 16 cm

Shock

0-3 mA, timer 0-10 sec, square pulse

Shock Delivery

Footswitch

Order # Model

Product

BH2 76-0006 LE830*

Aron Test Box

* Shock generator (BH2 76-0159) must be ordered separately.

Key Features

➤ An elegant and economical solution for screening anxiolytic drugs in mice ➤ Punishment based conflict test ➤ Shock with adjustable intensity

Parameters Measured

➤ Number of punished crossings

Components Included

Citations Foreman MM et al. (2009) Anxiolytic effects of lamotrigine and JZP-4 in the elevated plus maze and in the four plate conflict test. Eur J Pharmacol. 602(2-3):316-20. (mouse, USA) Jacobsen JP et al. (2008) SK3 K+ channel-deficient mice have enhanced dopamine and serotonin release and altered emotional behaviors. Genes Brain Behav. 7(8):836-48. Masse F et al. (2008) Anxiolytic-like effects of DOI microinjections into the hippocampus (but not the amygdala nor the PAG) in the mice four plates test. Behav. Brain Res. 188(2):291-297 (mouse, France) Mirza NR et al (2008) NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-biphenyl-2carbonitrile], a unique subtype-selective GABAA receptor positive allosteric modulator: in vitro actions, pharmacokinetic properties and in vivo anxiolytic efficacy. J Pharmacol Exp Ther. 327(3):95468. (mouse, Denmark) Masse F et al. (2007) Anxiolytic-like effect of 5-HT2 ligands and benzodiazepines co-administration: Comparison of two animal models of anxiety (the four-plate test and the elevated plus maze). Behav. Brain Res. 177(2):214-226 (mouse, France) Petit-Demouliere B and Bourin M (2007) Temporal parameters of one-trial tolerance to benzodiazepines in four-plate test-retest. Behav. Brain Res. 183(2):222-225. (mouse, France) Petit-Demouliere B et al. (2007) Factors triggering abolishment of benzodiazepines effects in the fourplate test-retest in mouse. Eur. Neuropsychopharmacol. In press (mouse, France) Masse F et al. (2007) Effect of GABAergic ligands on the anxiolytic-like activity of DOI (a 5-HT(2A/2C) agonist) in the four-plate test in mouse. Eur. Neuropsychopharmacol.;17(6-7):483-91 (mouse, France)

➤ Aron box

➤ Control unit footswitch ➤ SeDaCom software

➤ Cables and connectors ➤ Instruction manual ➤ 2 year warranty

Aron Test The Aron Test, or Four Plates Test, is an animal model of anxiety in which the exploration of the novel surroundings is suppressed by the delivery of a mild electric foot shock. The apparatus consists of a cage floored by four identical rectangular metal plates (8 x 11 cm) separated from one another by a gap of 4 mm. The plates are connected to a shocker unit that can generate electric foot shocks. Following habituation period, the animal is subjected to an electric shock when crossing (transition) from one plate to another, i.e. two legs on one plate and two legs on another. Boissier et al. 1968 has described this test first. The number of punished crossings is generally calculated for a period of 60 seconds. A substance with anxiolytic properties induces an increase in the number of punished passages.

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Anxiety & Depression Black and White Test Black and White Box

Black and White Test The Panlab/Harvard Apparatus Black and White Box allows easy and quick evaluation of an animal’s anxiety as reflected in their behavior. The test identifies behavioral modifications resulting from pharmacological agents. The Black and White Box assesses the animal’s displacement in two compartments with different sizes, color, and illumination. The Panlab/Harvard Apparatus experimental box, constructed of perspex, is composed of a small black compartments and a larger white compartment separated by a connecting gate. Each compartment has its own removable perspex floor of the same color of the respective walls and 90 X 90 mm sectors delimited by lines. The compartments are independently illuminated: the white one with a 100 W white bulb and the black one with a 40 W red bulb. Both bulbs are 370 mm from the floor of the box. The Panlab/Harvard Apparatus Black and White Box can be supplied with a weight transducer system for automated animal detection and photocell beams for evaluation of general activity during the test. The automated experimental chambers (up to 8) are associated to the PCbased control software PPCWIN for data storage and analysis.

Order # Model

Product

Key Features

BH2 76-0007 LE810

Experimental Chamber for Mouse

BH2 76-0008 LE816

Automated Experimental Chamber for Mouse: with Weight Transducer

➤ Can be associated with weight transducer technology for optimal animal detection

BH2 76-0009 LE812

Experimental Chamber for Rat

BH2 76-0010 LE818

Automated Experimental Chamber for Rat: with Weight Transducer

BH2 76-0011 PPCWIN

Software for Chamber Control and Data Analysis (8 Units)

➤ Compartments with independent and highly contrasted illumination ➤ Easy to clean between trials

➤ Easy connection to a PC through RS-232 port

Parameters Measured

➤ Total time spent in each compartment latency to the first change of compartment (regardless to the animal initial position) ➤ Number of changes between the black and white compartments ➤ Total duration of the experiment

Citations Lopez-Aumatell R et al (2007) Fearfulness in a large N/Nih genetically heterogeneous rat stock: Differential profiles of timidity and defensive flight in males and females. Behav. Brain Res. 188(1):41-55 (rat, Spain) Gimenez-llort L el al. (2002) Mace lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur. J. Neurosci. 16(3): 547. (mice, Spain, Sweden)

Components Included ➤ Experimental chamber

➤ Cables and connectors ➤ Instruction manual ➤ Set of spare fuses ➤ 2 year warranty

Options

➤ PPCWIN Software to control up to 8 automated boxes simultaneously

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Anxiety & Depression Vogel Test Vogel Test Set

Vogel Test The Vogel test has become a standard for fast screening the potential anxiolytic properties of drugs. In this procedure, the drinking behavior is punished by mild shocks leading to a significant reduction of water consumption in deprived animals. Drinking responses are then reestablished using drugs with anxiolytic properties. The Panlab/Harvard Apparatus Vogel test consists of a standard home cage associated with a grid floor. An electronic unit associated with a special nipple ensures the detection and counting of the licks reflecting the animal drinking behavior. Using an exclusive nipple design, any casual and non-specific contacts of the animal with the nipple will not be considered as a drinking response.

Vogel Shocker

A multi-cage configuration allows performing the Vogel test for up to 32 cages. The cages are associated with a LinkBox (1 for each 8 cages) ensuring the functional interaction between the lick sensor system, the LE10025 Shock generator (1 per cage) and the PackWin software for advanced protocol configuration and data acquisition. The interconnection among the cages and the computer is carry out by a RS-232 serial communication.

Specifications

Key Features

LE3208

Internal memory for up to 99 trials

LE10025

Shocker intensity: from 0.1 to 2 mA; duration: from 0.1 to 10 sec

Order # Model

Product

➤ Up to 32 cages can be associated with a computer

BH2 76-0316 LE862

Vogel Test Set (Excluding Control Unit)

BH2 76-0156 LINKBOX01

Link Box Interface for up to 8 Cages

➤ Total number of licks per trial

BH2 76-0002 PACKWIN

Software to Control up to 32 Cages

Components Included

BH2 76-0334 LE10025

Shock Generator with Scrambler (1 per Cage) Plus Lick Detector

BH2 76-0319 LE8624

Vogel Test Nipple Plus Bottle

BH2 76-0320 LE8626

Electric Contacts for Nozzle and Grid

➤ Allows Vogel experiments directly into the animal's home cage ➤ Exclusive nipple system to exclude non-specific contacts

Parameters Measured

➤ Total number of shocks received per trial ➤ Cage with lick detector

➤ Bottle with special nipple ➤ Cables and connectors

OPTIONS

➤ Instruction manual ➤ 2 year warranty

Options

➤ LinkBox01 interface for to 8 cages

➤ PackWin software to control up to 32 cages

➤ LE10025 Shocker unit with scrambler (0-2mA output) plus lick detector

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Anxiety & Depression Tail Suspension Test Tail Suspension Test

Key Features

➤ Fast evaluation of antidepressive, psychotropic drugs based on L. Steru and R.D. Porsolt based models ➤ Up to 6 mice monitored at the same time ➤ Automatic measurement of immobility ➤ Capable of automatic randomization

➤ Reanalysis enhanced, immobility threshold can be readjusted ➤ Direct exportation of the results into Excel ➤ Calculates energy and power in motion

Parameters Measured ➤ Immobility time ➤ Power

Components Included

➤ Transducers and electronic elements

➤ 1 set of 3 perpex compartments with adjustable floor height ➤ Cables and connectors ➤ Instruction manual ➤ 1 year warranty

Tail Suspension Test The automatic tail-suspension test allows a fast and reliable screening of the psychotropic properties (anti-depressants, sedatives) of drugs.

Specifications Material Composition

Black and white perspex, metal hook

Computer Requirements

Windows® XP, one or two free USB 2.0 slots

Maximum Number of Stations

6 per computer

Power Supply Standard

110 V/220 V, 50/60Hz, special plugs on request

Order # Model

Product

BH2 76-0490 BSTST2

Set of 3 Boxes, Including Transducers a nd Electronic Elements

BH2 76-0492 BSTST2LOG

Interface and Software for BSTST2CA

Citations Païzanisa E et al. (2009) Behavioural and neuroplastic effects of the new-generation antidepressant agomelatine compared to fluoxetine in glucocorticoid receptor-impaired mice. Int J Neuropsychopharmacol. 24:1-16. Dowiea MJ et al. (2009) Altered CB1 receptor and endocannabinoid levels precede motor symptom onset in a transgenic mouse model of Huntington's disease. Neuroscience. 29;163(1):456-65. Blondeau N et al. (2009) Subchronic Alpha-Linolenic Acid Treatment Enhances Brain Plasticity and Exerts an Antidepressant Effect: A Versatile Potential Therapy for Stroke. Neuropsychopharmacol. (mouse, France) In Press. Pang TYC et al. (2009) Altered serotonin receptor expression is associated with depressionrelated behavior in the R6/1 transgenic mouse model of Huntington's disease. Hum. Mol. Gen. 18(4):753-766. (mouse, Australia) DiNunzio JC et al. (2008) CNS Disorders—Current Treatment Options and the Prospects for Advanced Therapies. Drug. Dev Ind. Pharm. 13:1-27. (mouse, USA) Popa D et al. (2008) Lasting Syndrome of Depression Produced by Reduction in Serotonin Uptake during Postnatal Development: Evidence from Sleep, Stress, and Behavior. The Journal of Neuroscience, 28(14):3546-3554. (muse, France) Renoir T et al. (2008) Differential long-term effects of MDMA on the serotoninergic system and hippocampal cell proliferation in 5-HTT knock-out vs. wild-type mice. Int J Neuropsychopharmacol. 2008 Jul 9:1-14. (mouse, France) Castagné V et al. (2007) UNIT 5.8 Rodent Models of Depression: Forced Swim and Tail Suspension Behavioral Despair Tests in Rats and Mice. Current Protocols in Pharmacology. 38:5.8.1-5.8.11. © 2007 by John Wiley & Sons, Inc. Crozatier C et al. (2007) Calcineurin (protein phosphatase 2B) is involved in the mechanisms of action of antidepressants. Neuroscience. 144(4):1470-1476. (Mouse, France) Vogt MA et al. (2007) Suitability of tamoxifen-induced mutagenesis for behavioral phenotyping. Experimental Neurology 211(1):25-33. (Mouse, Germany) Alexandre C et al. (2006) Early Life Blockade of 5-Hydroxytryptamine 1A Receptors Normalizes Sleep and Depression-Like Behavior in Adult Knock-Out Mice Lacking the Serotonin Transporter. J. Neurosci. 26(20): 5554-5564. (mouse, France, Germany) Chourbaji S et al. (2006) IL-6 knockout mice exhibit resistance to stress-induced development of depression-like behaviors. Neurobiology of Disease 23(3):587-594. (Mouse, germany) Meziane H et al. (2006) Estrous cycle effects on behavior of C57BL/6J and BALB/cByJ female mice: implications for phenotyping strategies. Genes, Brain and Behavior. 6(2):192-200. (mouse, France) Cryan JF et al. (2005) The tail suspension test as a model for assessing antidepressant activity: Review of pharmacological and genetic studies in mice. Neurosci. Biobehav. Rev. 29(4-5): 571-625 (mouse; Switzerland, USA) Mombereau C et al. (2004) Genetic and Pharmacological Evidence of a Role for GABAB Receptors in the Modulation of Anxiety- and Antidepressant-Like Behavior. Neuropsychopharmacol. 29:1050-1062 (mouse, Stwitzerland) Strekalova T et al. (2004) Stress-Induced Anhedonia in Mice is Associated with Deficits in Forced Swimming and Exploration. Neuropsychopharmacol. 29:2007-2017 (mouse, Germany)

The measuring principle is based on the energy expended by mice trying to escape from their suspension. During the test, the movements are analyzed in terms of force, energy and power developed over time. A complete system includes the suspension cages (3 mice or 6 mice at a time) and a USB based user-friendly software to run, record, analyze and replay the experiments. The results are either printed or stored in .xls file formats.

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Reward & Addiction Guide

Addiction is a state in which an organism engaged in a compulsive behavior which is reinforced or rewarded, even when faced with negative consequences.

A distinction is generally made between “reward” and “addiction”. “Reward” is defined as a biological mechanism mediating behavior motivated by events commonly associated with pleasure. Reward and motivation can be considered as natural components of normal behavior. Indeed, reward pathways clearly serve to direct behavior towards goals that are beneficial to the organism or species survival, e.g. food and water intake, reproductive activities and others. However, a pleasurable substance can lead to “addiction”, inducing a compulsive behavior or substance-seeking and intake, a loss of control of limiting intake and the emergence of a negative emotional state when access to the substance is prevented. A variety of substances are susceptible to provoke addiction, such as alcohol, illicit drugs, nicotine, and others.

Given that drug abuse is major health problem calling new therapeutic (some animal models have been developed) in order to study behavioral and neurobiological basis of addiction. Actual rodent models have predictive validity and are reliable for the study of the addictive potential of substances, the mechanism underlying the transition from drug use to addiction and the relapse or the individual vulnerability phenomenon.

From a mechanistic point of view, drug addiction is a chronic, relapsing disease that is induced by disturbances in the neurobiological mechanism of brain function. The use of substances for recreational purposes is based on the fact that they cause rewarding effects through the pleasure center of the brain, mainly represented by the mesocorticolimbic dopaminergic pathways. Chronic drug abuse, however, is associated with a range of adaptive changes in brain physiology. These alterations, which appear to be both intrinsic and extrinsic to the rewarding pathways, gradually lead to the addictive disorder.

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Reward & Addiction Guide Behavioral Test

Behavioral Test

Locomotor Response to Novelty

Conditioned Place Preference

Locomotor responses to novelty has been shown to represent a predictive factor for the addictive properties of drugs or vulnerability to a drug treatment. Indeed, in an animal model for vulnerability to drug abuse, animals that exhibit greater motor activity in a novel environment (high responders; HR) are found more sensitive to drugs of abuse and are more likely to self-administer these drugs compared to less reactive animals (low responders; LR). In the light of clinical evidence between drug abuse and mood disorders, this model is widely used to investigate whether individual differences in locomotor reactivity to novelty are related to anxiety and depression-like responsiveness in rodents.

The purpose of the Conditioned Place Preference test is to characterize the rewarding potential of a drug or other experimental condition. The procedure involves operant conditioning of a preference for a particular environment that has been consistently paired with a subjective internal state induced by the tested substance or condition. If a drug has marked rewarding properties, the animal will spend more time in the compartment with which it was paired when subsequently tested without the drug. The Conditioned Place Preference procedure is classically used for a long duration to test the addictive liability of a drug for addictive properties for both research and pharmaceutical studies. The procedure may also be modified to determine whether genetically modified animals are more or less sensitive to the reinforcing effects of a drug.

Reasons for Choosing This Test ➤ Explore novelty-seeking behavior ➤ Free exploration paradigm ➤ Test maximizing avoidance/anxiety-related behavior respect to approach/exploratory behavior ➤ Only one exposure (no habituation) and quickly performed ➤ Easy-to-do for inexperienced users ➤ Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Anxiogenic conditions (novel environment with no possibility of escape)

Related Human Disease/Applications ➤ ➤ ➤ ➤

Drug Screening Phenotyping Addiction Anxiety Disorders

Reasons for Choosing This Test ➤ Detects putative reinforcing properties of drugs ➤ Involves associative learning ➤ Used for both mice and rats

Reasons for Not Choosing This Test ➤ Positive results do not imply that the animal will develop a drug addiction (e.g. will display self-administration behavior) ➤ The drug is given to the animal by the experimenter ➤ Long and laborious procedure ➤ Need highly controlled experimental conditions (noise, light, odor, handling) ➤ Changes in behavioral output can be brought by many cognitive and non-cognitive factors, such as alteration of learning, locomotor activity, and vision

Related Human Disease/Applications ➤ ➤ ➤ ➤

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Drug Screening Compulsive Behaviors Phenotyping Drug Dependence

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Reward & Addiction Guide Behavioral Test

Behavioral Test

Self Administration

Food-Motivated Operant Conditioning

Self Administration is a classic model of human drug taking behavior and consists of establishing an operant conditionng of an instrumental response (nose-poke, lever pressure) to obtain a reward, according to a fixed or progressive ratio. Self administration is a standard paradigm for studying the acute rewarding properties of a drug, the development of habitual drug-seeking behavior, and ultimately, addiction. This method can be used to assess the abusive potential of a drug.

Reasons for Choosing This Test ➤ Drug self-administered by the animal itself ➤ Involves associative learning and operant conditioning ➤ Robust performance and specific responses ➤ Used for both mice and rats

Reasons for Not Choosing This Test ➤ Long and laborious procedure ➤ Requires animal surgery ➤ Changes in behavioral output can be brought by many cognitive and non-cognitive factors, such as alteration of learning, locomotor activity and vision

Related Human Disease/Applications ➤ ➤ ➤ ➤

Drug Screening Phenotyping Drug Dependence Alcohol Dependence

Progressive-ratio (PR) schedules permit studying food-motivated behavior. These schedules require an increasing number of operant responses to obtain successive rewards within a session. For example, a typical PR 5 schedule requires five responses to produce the first reinforcer and the response requirement is incremented by five each time a reinforcer is earned. The breaking point, defined as the highest ratio completed is a classic measurement reflecting the efficacy or motivational strength of food, and is increased in response to food deprivation or a reward of high palatability.

Reasons for Choosing This Test ➤ Sensible to fine modifications in feeding behavior that can not always be assessed under free-access conditions ➤ Sensitive for both mice and rats

Reasons for Not Choosing This Test ➤ Requires food deprivation ➤ Laborious procedure: may require many sessions of learning ➤ Influenced by any alteration in learning process

Related Human Disease/Applications ➤ Drug Screening ➤ Phenotyping ➤ Anhedonia

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Reward & Addiction Place Preference Box Place Preference Box

Place Preference Box Panlab/Harvard Apparatus Place Preference Box is a standard experimental chamber for automated assessment of conditioned place preference and aversion in rodents, two tests widely used for screening the reinforcing properties of drugs (or natural stimuli) as well as for investigating the brain neurobiological systems implicated in reward and addition. The experimental box consists of two perspex compartments of the same size interconnected by a central grey corridor. The compartments can be differentiated by both visual and tactile cues: the color of the walls in each compartment (white or black) and the texture of the floors (smooth or rough). The box is provided with transparent front walls which may be covered with extractable opaque covers (included). Manually operated sliding doors are provided to manage the access to the two compartments from the corridor. The experimental box can be supplied with or without automatic animal position detection system. The automated animal position detection is carried out by a weight transducer system which is associated to the PC-based control software PPCWin.

Key Features

➤ Allows a combination between the visual and tactile cues defining each compartment

➤ Weight transducer technology allows animal detection optimization in low-contrast conditions

➤ Software for automated storage and analysis of the data

➤ Up to 8 stations can be connected at once to PC through a single cable

Parameters Measured

➤ Total number of entries into the compartments

➤ % distribution of the entries into different compartments ➤ Permanence time in each compartment

➤ % permanence time in respect to the total duration ➤ Chronological sequence of animal displacements

Components Included

➤ Place preference box with removable floors

➤ PPCWIN software (for automated animal position detection) ➤ Instruction manual

➤ Opaque extractable wall covers

Options

➤ SMART video-tracking system

Specifications Experimental Box Dimensions: Rat Compartments

300 (W) x 300 (D) x 340 (H) mm; corridor: 80 (W) x 100 (D) x 340 (H) mm; doors: 100 (W) x 140 (H)

Mouse Compartments

100 (W) x 130 (D) x 130 (H) mm; corridor: 72 (W) x 72 (D) x 130 (H) mm; doors: 60 (W) x 60 (H) mm

Position Detection Technique

Weight transducers

Material Composition

Perspex

Connection of Several Units to PC

Neither PC interface nor PC card are required. One cable connects all units to the PC.

Certifications

CE compliant

Power Requirement

110/220 V, 50/60 Hz

Order # Model Product BH2 76-0216 LE890

Standard Place Preference System for Rats

BH2 76-0217 LE891

Standard Place Preference System for Mice

BH2 76-0218 LE892

Automated Place Preference System for Rats Using Weight Transducers

BH2 76-0219 LE893

Automated Place Preference System for Mice Using Weight Transducers

BH2 76-0011 PPCWIN

Software Associated to Automated Boxes (up to 8 units)

OPTIONS

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BH2 76-0028 SMART

SMART Video-Tracking System (to be used with LE890 or LE891)

BH2 76-0029 SMART JUNIOR

Smart JUNIOR Video-Tracking JUNIOR (Requires SJPP)

BH2 76-0415 SJPP

Place Preference Module

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Reward & Addiction Spatial Place Preference Box

The apparatus consists of a box with two equally sized compartments interconnected by a rectangular corridor. The compartments are differentiated by the motifs painted on the walls (dots or stripes) and the color (different shade of grey tones, light or dark) and texture (smooth or rough) of the floor. The innovation of our box is the possibility to combine a new additional spatial dimension allowing the animal to differentiate the different compartments in a more discriminative manner. Transparent walls are also used to minimize the time the animal spent in the corridor. The introduction of these new discriminative elements allows:

Key Features

➤ Allows combination between the visual, tactile and spatial cues defining each compartment ➤ Optimize the differentiation between compartments

➤ Minimize initial place preference during pre-test phase ➤ Transparent walls to minimize time in corridor ➤ Video-tracking system optimizes detection

Parameters Measured

➤ Total number of entries into compartments

➤ % distribution of entries into different compartments ➤ Permanence time in each compartment

Optimizing the results obtained in the place preference and aversion paradigms (low variability in the response, reduced number of animals per group)

Organizing the discriminative elements in a wide variety of configurations for studies evaluating spatial or contextual memory

Using the elements as discriminative cues associated with drug exposure in diverse other experimental designs.

The Panlab/Harvard Apparatus spatial place preference box can be associated with the SMART video-tracking system for detection and analysis of animal position throughout the test or PPCWIN, see page 100.

Specifications Reversible Floor Textures

One side rough, one side smooth

Box Dimensions for Mice: Total (ext.)

46 (w) x 27 (d) x 25 (h) cm

Compartments (int.)

20 (w) x 18 (d) x 25 (h) cm

Aisle (int.)

20 (w) x 7 (d) x 25 (h) cm

Box Dimensions for Rats:

➤ % permanence time in respect to the total duration

Total (ext.)

88 (w) x 47 (d) x 45 (h) cm

Compartments (int.)

40 (w) x 34 (d) x 45 (h) cm

Components Included

Aisle (int.)

25 (w) x 13 (d) x 45 (h) cm

➤ Chronological sequence of animal displacement ➤ Spatial Place Preference Box

Walls Width

➤ 4 parallel piped triangles (two colored in stripes, the other two in dots)

Order # Model

Product

BH2 76-0278 LE895

Spatial Conditioned Place Preference for Mice

BH2 76-0279 LE897

Spatial Conditioned Place Preference for Rats

BH2 76-0376 LE896

Spatial Place Preference Mice-Position Detection Weight Cells

BH2 76-0441 LE898

➤ Smart JUNIOR Video Tracking System

Spatial Place Preference Rats-Position Detection Weight Cells

BH2 76-0011 PPCWIN

PPCWIN Software (to be used with LE896/LE898)

Spatial Place Preference Box

BH2 76-0028 SMART

SMART Video-Tracking System (to be used with LE895 or LE897)

BH2 76-0029 SMART JUNIOR

Smart JUNIOR Video-Tracking JUNIOR (Requires SJPP)

BH2 76-0415 SJPP

Place Preference Module

➤ 2 reversible floors (one dark grey, one light grey)

➤ 2 three sided pyramids (one colored in stripes, the other in dots) ➤ 2 sliding doors (one with stripes, one with dots)

Options

➤ SMART Video Tracking System

The Panlab/Harvard Apparatus spatial place preference box is an experimental chamber developed with the aim to optimize place preference and aversion studies in small laboratory animals, especially mice. The design of the box is based on a close collaboration with prominent Professors Dr. Rafael Maldonado and Dr. Olga Valverde from the Laboratory of Neuropharmacology in Barcelona, Spain.

OPTIONS

6 mm

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Reward & Addiction PPCWIN Software

Related Hardware

➤ Place Preference Box, see page G60

➤ Spatial Place Preference Box, see page G61 ➤ Black & White Box, see page G57

PPCWIN Software PPCWIN is an easy-to-use software for monitoring Conditioned Place Preference (or aversion) tests and Black and White experiments (for anxiety). It has been specially designed to work with the Panlab/Harvard Apparatus Automated Place Preference and Black and White boxes equipped with weight transducers for the automatic detection of animal position.

software species is hardware specific

Key Features

➤ Easy-to-use software for standard conditioned place preference experiments

➤ For both place preference and black and white experiments ➤ A test mode enables immediate checking of the communication between the software and the experimental chambers

➤ Current animal position can be visualized in real-time during the acquisition of data ➤ Provides integrated results

➤ Tables of result easily exportable in Excel format for further analysis ➤ RS-232 or USB port direct connection

Parameters Measured

➤ Total number of entries into the black, white and grey compartments

➤ % distribution of entries into the different compartments

PPCWIN controls independently up to 8 experimental chambers. The system includes a test mode enabling immediate and reliable checking of the communication between the software and the experimental chambers. The Place Preference and Black and White boxes are basically divided in two different compartments connected by a grey corridor/door, respectively. One experiment can be composed of several sessions, depending on the number of experimental groups and animals per group used in the study. PPCWIN is easy to configure as the user only needs to enter the desired duration of experiment and some specific information about the session (subject name, group, etc). During data acquisition, information about protocol state, animal position and current data can be visualized for each cage on the corresponding control window. PPCWIN provides a raw data table with all the standard parameters for conditioned place preference and black and white experiments (permanence time in the compartments, number of entries, etc.) and a detailed chronological sequence of animal displacements for each session. A report table can be generated containing the results from different stored session. Data from the tables of result can be easily exported in formats widely used to perform complementary analysis.

Specifications Computer Requirements

2 GHz processor or higher (Celeron processor not supported), 2 Gb of RAM, 1 free USB for the protection key; 1 free RS-232 serial port for boxes connection (a USB-Serial adapter included in the software pack can be used when a RS-232 serial port is not available)

Graphic Card Requirements

256 colors palette graphics card for 1024x768 pixels, 32-bit true color RGB display

Components Included

System Requirements

Windows® XP (SP2 or Higher), Vista 32 – PC integrated standard sound card (DirectX compatible)

➤ Cables and connectors

Order # Model

Product

BH2 76-0011 PPCWIN

PPCWIN Software for up to 8 Boxes

➤ Permanence time in each compartment

➤ % permanence time in respect to the total experimental duration

➤ Chronological sequence of animal displacements

➤ Latency to the first transition regardless to the initial position ➤ Experiment duration ➤ Software CD

➤ Instruction manual

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Reward & Addiction Self Administration Box

The chamber is assembled with black aluminum walls and a transparent front door. The chambers employ a stainless-steel grid floor that allows waste to collect in a removable tray. All floor components (including the grid) are removable for systematic cleaning. Special modules are available for self-administration and selfstimulation procedures: lever or nose-spoke, food or drink dispensers, drug delivery system and stimuli (light, sound, shock, etc.). Each chamber is associated with a LinkBox which provides power to up to 8 (expandable to 16) self-administration modules conferring to the chambers a full autonomy. Only one cable connects the LinkBox to the PC, this last for advanced protocol configuration and running. All Panlab/Harvard Apparatus self-administration boxes are associated with the potent and versatile Packwin software which allows configuring any kind of user-defined schedules (training, priming, fixed-ratio, progressive ratio, extinction, relapse, etc.) and providing relevant data in this context (number of pressing on active and inactive levers, number of injection received, pattern response graph etc.) Packwin must be ordered separately.

Key Features

➤ Entirely modular box

➤ Easily removable waste tray

Order # Model

Product

BH2 76-0151 LE1002

Modular Operant Chamber, Mice

➤ Associated with PackWin software

BH2 76-0152 LE1005

Modular Operant Chamber, Rat

➤ Reduced number of cables

BH2 76-0153 LE100201

Mice Shockable Grid

➤ Neither PC interface nor PC cards are required

BH2 76-0154 LE100501

Rats Shockable Grid

Parameters Measured

BH2 76-0156 LINKBOX01

Link & Power Supply for up to 8 Chamber Modules. RS-232 Output

BH2 76-0157 LE26

Sound-proof Box

BH2 76-0002 PACKWIN

Multipurpose Behavior Software for up to 8 LINKBOX 01

BH2 76-0342 LE100265

Lever for Mice

➤ Cumulative curve graph

BH2 76-0360 LE100565

Lever for Rats

BH2 76-0341 LE100264

Retractable Lever for Mice

Components Included

BH2 76-0359 LE100564

Retractable Lever for Rats

BH2 76-0343 LE100267

Light Stimuli for Mice

BH2 76-0361 LE100567

Light Stimuli for Rats

➤ Cables and connectors

BH2 76-0331 LE100242

Adjustable Buzzer for Mice

BH2 76-0350 LE100542

Adjustable Buzzer for Rats

Options

BH2 76-0347 LE100290

Acoustic Stimulus (Buzzer) for Mice

BH2 76-0365 LE100590

Acoustic Stimulus (Buzzer) for Rats

➤ Wide range of modules

BH2 76-0335 LE100250

Pellets Dispenser w/Feeder for Mice

➤ Sound attenuating box

BH2 76-0353 LE100550

Pellets Dispenser w/Feeder for Rats

➤ PackWin software

BH2 76-0336 LE100251

Photoelectric Detector of Access (Feeder & Drink & Nose Poke) for Mice

Self Administration Box

BH2 76-0354 LE100551

Photoelectric Detector of Access (Feeder & Drink & Nose Poke) for Rats

BH2 76-0159 LE10026

Shock Generator with Scrambler, 0-2 mA Output

BH2 76-0162 LE1015

Harness Set for Drug Administration

BH2 76-0160 LE1010

Harness Set for Electrical Stimulation

BH2 76-0161 LE12605

Electrical Stimulator (Auto-Stimulation)

➤ Number of responses (lever pressing or nose-spoke) ➤ Response rate

➤ Number of reinforcement received

➤ Number of responses during drug injection & time-out ➤ User-defined parameters capabilities ➤ Reponse pattern graph ➤ Experimental chamber ➤ Instruction manual ➤ 2 year warranty

➤ Linkbox (power connection box for up to 8 modules)

The Panlab/Harvard Apparatus self-administration box is an entirely modular experimental enclosure designed to conduct a wide variety of different schedules for studying reward and addiction in laboratory animals.

OPTIONS

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Food and Drink/Metabolism Guide Metabolism is the set of chemical reactions that occur in living organisms in order to maintain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Body weight in adults is normally stable over the course of months to years. This stability in body weight occurs despite large fluctuations in caloric intake, thus demonstrating that energy intake and energy expenditure are finely regulated. Indeed it has been shown that changes in body weight result in compensatory modifications in energy expenditure which attempt to return body weight to the baseline value. In a similar way, the composition and volume of body fluids is submitted to a fine regulation in order to maintain a water balance, which is essential for the survival and function of a living organism. However, the human body does not store water in the way that it stores calories (as glycogen or body fat), so a constant daily supply is needed. Metabolism is usually divided into two categories. Catabolism breaks down large molecules for example to harvest energy in cellular respiration. Anabolism, on the other hand, uses energy to construct components of cells such as proteins and nucleic acids. Specific proteins (enzymes and hormones) in the body control the chemical reactions of metabolism, and each chemical reaction is coordinated with other body functions. In fact, thousands of metabolic reactions happen at the same time – all regulated by the body – to keep the cells healthy and working. After food is eaten, molecules in the digestive system, called enzymes, break proteins down into amino acids, fats into fatty acids, and carbohydrates into simple sugars (e.g. glucose). In addition to sugar, both amino acids and fatty acids can be used as energy sources by the body when needed. These components are absorbed into the blood, which transports them to the cells. After they enter the cells, other enzymes act to speed up or regulate the chemical reactions involved with “metabolizing” these compounds. During these processes, the energy from these compounds can be released for use by the body or

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stored in body tissues, especially the liver, muscles, and body fat. In this way, the process of metabolism is really a balancing act involving two kinds of activities that go on simultaneously – the building up of body tissues and energy stores and the breakdown of body tissues and energy stores to generate more fuel for body functions.

This tight regulation of intake and expenditure is mediated by the central nervous system. This regulation needs a constant monitoring of the balance (intake, expenditure, storage) integrated by the hypothalamus that receives information through metabolic, neural and hormonal signals. Any dysfunctions in these systems may lead to important metabolism disorders such as diabetes, anemia, hyper/hypo-thyroidism and eating disorders such as obesity and anorexia. These disorders are considered a serious and growing public health problem and research laboratories, pharmaceutical companies as well as psychologists are seeking to develop adequate therapeutic strategies for these and other conditions.


Food and Drink/Metabolism Guide Behavioral Test

Behavioral Test

Indirect Calorimetry

Food and Drink Intake

Knowledge in the field of animal energy expenditure is largely based upon indirect calorimetry, which is estimation of metabolic heat production by the organism from measurements of indices such as oxygen consumption or carbon dioxide production.

Major health problems linked to food and drink intake, such as alcoholism and obesity, the search to define the role of brain and molecular mechanisms in regulating food and drink intake has taken on a new priority. Food intake consists of meal size multiplied by meal number which constitutes a feeding pattern. Specific analysis of these parameters is of particular interest since they are controlled by distinct brain areas and neurochemical messengers and reflect different physiological significance (meal size relates to satiation, whereas meal number relates to satiety). Moreover, drinking has generally not been considered in meal definition, a close temporal relationship exists between eating and drinking. In this way, a precise monitoring of food and drink intake (amount and meal pattern analysis) along the circadian circle is necessary to evaluate fine alterations of these functions, in response to treatments, brain lesions or genetic manipulations. Food and drink intake is a parameter that can be evaluated together with indirect calorimetry in metabolism studies.

For the purpose of most energy-expenditure studies, indirect calorimetry consists of measuring the volume of expired air per unit of time and determining the percentage of oxygen utilized. This data is then used for estimating the metabolic rate (energy expenditure) and the respiratory exchange ratio (relative measurement of fat, carbohydrate and protein oxidation). Indirect calorimetry studies are generally accomplished by utilizing sophisticated systems whereby the amount of oxygen consumed and carbon dioxide produced by an animal is precisely measured over a period of time. These systems consist of cage (chambers), air pumps, air flow controllers, valves, and a gas analyzer all controlled by a potent software for the acquisition, storage and analysis of the data. Indirect calorimetry can be evaluated together with food and drink intake and activity in metabolism studies.

Reasons for Choosing This Test Reasons for Choosing This Test ➤ Studies energy intake and expenditure in small laboratory animals ➤ Non-invasive technique ➤ Entirely automated procedure ➤ Indirect evaluation

Reasons for Not Choosing This Test ➤ Needs sophisticated equipment ➤ Needs expertise for correct use ➤ May be influenced by temperature, humidity, ambient air changes (controlled environments are recommended)

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤

Obesity Bulimia Anorexia Diabetes Drug Screening Phenotyping

➤ Allows studying intake amount and meal pattern along the day/night circle ➤ Intake measurements can be automated

Reasons for Not Choosing This Test ➤ Laborious procedure if done manually ➤ Not all the automated equipment commercially available allow a precise evaluation of intake, specifically in mice

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤

Obesity Bulimia Anorexia Diabetes Drug Addiction Alcohol Dependence Drug Screening Phenotyping

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Food and Drink/Metabolism Guide Behavioral Test

Behavioral Test

Treadmill Test

Food-Motivated Operant Conditioning

The treadmill test in rodents is a useful tool with great value in the study of functional capacity and is a validated standard model for investigations in the field of human metabolism. A subject is forced to walk/run on a treadmill (adjustable speed and inclination) during specific periods of time. This test allows the study of various physiological and behavioral functions such as long and shortterm effort during exercise, locomotion, metabolic exchanges, cardiac function, motor coordination and fatigue.

Reasons for Choosing This Test ➤ Adapted from a human test ➤ Allows the researcher to precisely control the level of exertion ➤ Easy-to-do (for inexperienced users) ➤ Applicable for mice and rats

Reasons for Not Choosing This Test ➤ Needs repetitive daily exposures for training on the apparatus ➤ Requires constant vigilance by the researcher to ensure the animal runs for the experimental duration ➤ Use of aversive stimuli to encourage running

Progressive-ratio (PR) schedules permit studying food-motivated behavior. These schedules require an increasing number of operant responses to obtain successive rewards within a session. For example, a typical PR 5 schedule requires five responses to produce the first reinforcer and the response requirement is incremented by five each time a reinforcer is earned. The breaking point, defined as the highest ratio completed is a classical measure reflecting the efficacy or motivation strength of food and is increased in response to food-deprivation or reward high palatability.

Reasons for Choosing This Test ➤ Sensible to fine modifications in feeding behavior that can not always be assessed under free-access conditions ➤ Sensitive enough for both mice and rats

Reasons for Not Choosing This Test ➤ Requires food deprivation ➤ Laborious procedure and requires many sessions to train the subjects ➤ Influenced by any alteration in learning process

Related Human Disease/Applications ➤ ➤ ➤ ➤ ➤

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Oxidative Stress Diabetes Parkinson’s Disease Ischemia Osteopenia/Osteoporosis

Related Human Disease/Applications ➤ Drug Screening ➤ Phenotyping ➤ Anhedonia

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Food & Drink/Metabolism Oxylet System

Modular System for Respiratory Metabolism, Food/Drink Intake and Activity in Rodents BH2 76-0451 Home Cage for Rat and Mouse

Key Features

➤ Extremely compact “built-in” system ➤ Same system for rats and mice

➤ Laser sensor greatly reduces the influence of air humidity and temperature on measurements ➤ Independent air flow control in each cage

➤ Highly accurate and stable monitoring of the food and drink consumption and activity due to the use of newly adapted weight transducer technology ➤ Autoclavable experimental cages

➤ NEW! Option for respiratory metabolism measurements in neonates!

Respiratory Metabolism Monitoring The Oxylet is a modular system allowing the integration of respiratory metabolism (O2 consumption and CO2 production), food and drink intake, activity and rearing measurement in specifically adapted home cages in laboratory models. Respiratory metabolism is evaluated by means of indirect calorimetry an optimized system for studies in laboratory rodents (mice and rats). The system uses standard Allentown Caging Equipment (ACE) home cages which are fully autoclavable for easy cleaning. Air tight lids, grid floors, and food/drink dispensers are available as accessories to these home cages depending on the species to be used, mice or rats. Our specially designed lid easily converts the system for use with either rats or mice in the same home cage! The Oxylet system also consists of the air flow control unit, which allows a fine regulation of the air flow inside the chamber, is controlled independently for each connected cage. A total flow of 20 L/min can be obtained which will permit the user to conduct simultaneous experiments with different animal species and sizes – making our system the most flexible available!

BH2 76-0451 BH2 76-0452 BH2 76-0455 BH2 76-0459

From the air flow control unit, cage samples are sent to the most crucial component of the system – the gas analyzer. The gas analyzer, which contains a laser sensor for O2 and an infrared spectroscopy sensor for CO2, feature the highest level of quality with a 0.01% sensor resolution! Special Oxylet configuration is now available for performing calorimetry studies with rat neonates! Our optimized and validated technology includes specially designed metabolic chambers which account for smaller air volumes. Accurate sampling of this small flow is possible through fine adjustments of low air flow (0 – 2L/min) to obtain values for gases exchanged during the pup’s resting state. Specifically controlled air flow ensures sufficient time for the chamber gas equilibrium and for small changes in gas concentration created by the pup to be sampled. The Oxylet system can also be adapted with our rodent treadmills for exercise studies! Simply combine our air flow controller and gas analyzer with our single lane rat or mouse treadmills (see pages 27 to 28) and select the air tight lane option.

Food and Drink Intake Monitoring

Food and drink intake as well as activity are evaluated using the extensiometric weight transducer technology developed by Panlab/ Harvard Apparatus. These transducers and their associated amplifiers are mounted in a specially designed platform beneath each adapted home cage. This technology allows the continuous assessment of the animal food and drink consumption as well as spontaneous activity with the highest accuracy and stability. Food intake is monitored with an accuracy of 0.02g and drink with an accuracy of 0.01g fluid – the most sensitive intake monitoring commercially available for individual rodents! The base system home cages can be associated with 2 external dispensers – both food, both drink, or one of each – depending on researchers’ preference. Optional standard wire bar lids can be used for providing additional food and drink for non-monitored intake (for example, useful in preference studies of different drinks).

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Food & Drink/Metabolism Oxylet System (continued)

Modular System for Respiratory Metabolism, Food/Drink Intake and Activity in Rodents BH2 76-0451 BH2 76-0453 BH2 76-0455 BH2 76-0459

Specifications Oxygen Sensor Technology

Laser Diode Absorption

Measurement Range

0-100% (only limited by the hogh calibration point used)

Resolution

0.01%

Linearity

±0.2%

Noise

±0.03% (20 ms average)

Accuracy

±0.2% (24 hours)

Carbon Dioxide Sensor

Activity and Rearing Monitoring Continuous recording of spontaneous activity is easily monitored through the extensiometric weight transducers in the specially designed platform beneath each adapted home cage. This transducer technology allows detection of the animal’s movement without displacement to a high level of precision – even for the finest of mice movements! Rearing assessment requires simply two additional InfraRed (IR) frames connected to the system. Our optimized modular design provides easily expandability for any of the options of the system. The researcher can select only those components of initial interest but with the flexibility of adding any of the others at a later date. Our highly integrated system minimizes components to save valuable laboratory space, contains fewer cables between successive daisy-chained cages and is easier to clean and maintain. The built-in display shows real-time data for total amount of food and drink consumed, total activity, and total number of rearings for quick monitoring of experimental progress from the front of the system.

Panlab/Harvard Apparatus is proud to announce the newest addition to the Oxylet system – the Neonate Oxylet!

Our system has been modified to accommodate neonatal rats as small as 4 grams. A complete system would be the O2 and CO2 Gas Analyzer (LE405), Neonate air switching unit for 2 neonates (LE4002FLN), and either of the neonate chambers (NEO1 or NEO2). To expand the neonate system beyond 2 animals, you will also need the Extension Air Switching Unit (LE4004FLN) and the additional number of neonate chambers (up to a maximum of 32 animals). Please contact our technical support department for additional details and literature.

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Technology

InfraRed Spectroscopy

Measurement Range

0-10%

Resolution

0.01%

Accuracy

< 10% of reading between 5% - 10% CO2; < 0.3% absolute of reading < 5% CO2

LE405 Dimensions

260 (W) x 330 (D) x 120 (H) mm

LE405 Digital Output

RS-2332 Serial Port

LE405 Analog Signal Outputs

Connectors: Panel BNC female; Output O2: 10 mV/% O2 Range; Range O2: 0-1V; Output CO2: 100 mV+ (100 mV/%CO2); Range CO2; 0.1 – 1V

LE400FL Air Flow

0 to 20 l/min

LE400FLN Air Flow

0 to 2 l/min

LE400FL Switching

Cycle 2 to 4 chambers in an interval running from 1 to 999 seconds

Intake Amplifier Resolution

20 mg (for food and drink)

Intake Amplifier Drift

< 0.1 mg/day

Experimental Chamber Dimensions: Rat/Mouse

259 (D) x 234 (W) x 209 (H) mm

Rat Pup

215 and 550 ml

IR Frame

16 IR beams spaced 15.6 mm

Order # Model

Product

BH2 76-0426 LE4002FLN

Neonate Rat Air Switching Unit/Sample Pump - 2 animals

BH2 76-0427 LE4004FLN

Extension Neonate Rat Air Switching Unit/Sampling Pump – 4 animals

BH2 76-0428 NEO1

Neonate chamber, 215 ml

BH2 76-0429 NEO2

Neonate chamber, 550 ml

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Food & Drink/Metabolism Oxylet System (continued)

Modular System for Respiratory Metabolism, Food/Drink Intake and Activity in Rodents Order # Model

Product

BH2 76-0451 LE1301

Home Cage for Rat and Mouse (Requires accessories for species used)

BH2 76-0452 LE1302

Accessories for Rat (Air tight lid, grid floor, food and drink dispenser)

BH2 76-0453 LE1303

Cage Accessories for Mouse (Air tight lid, grid floor, food and drink dispenser)

BH2 76-0454 LE1304

Standard wire bar lid for standard pellets and bottle accessories

BH2 76-0080 METABOLISM

Metabolism Software Platform (up to 32 enclosures) Requires Metabolism Experimental Modules for calorimetry, food and drink intake, and/or associated activity and rearing

BASE SYSTEM

CALORIMETRY COMPONENTS BH2 76-0195 LE405

O2/CO2 Analyzer

BH2 76-0193 LE4002FL

Air Supply and Switching Unit for up to 2 Experimental Cages

BH2 76-0194 LE4004FL

Air Supply and Switching Unit for up to 4 Experimental Cages

BH2 76-0145 METAOXY

Metabolism Software Experimental Module – calorimetry

INTAKE COMPONENTS BH2 76-0455 LE1305

Platform with sensors and amplifiers for Food and Drink and Activity

BH2 76-0456 LE1306

Drinking bottle Rat/Mouse

BH2 76-0457 LE1307

Feeding Container Rat/Mouse

BH2 76-0081 METAINT

Metabolism Software Experimental Module – Food and Drink Intake

ACTIVITY COMPONENTS BH2 76-0455 LE1305

Platform with sensors and amplifiers for Food and Drink and Activity

BH2 76-0459 LE1308

IR Frame for Rearing Detection

BH2 76-0087 METAACT

Metabolism Software Experimental Module – Activity and Rearing Detection

Citations Franckhauser S et al. (2008) Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice. Dialectologia. 51(7):1306-1316 (mouse, Spain) Knauf et al. (2008) Brain Glucagon-Like Peptide 1 Signaling Controls the Onset of High-Fat DietInduced Insulin Resistance and Reduces Energy Expenditure. Endocrinology. 49(10): 4768-4777 (mouse, France) Bauche I et al. (2007) Overexpression of Adiponectin Targeted to Adipose Tissue in Mice: Impaired Adipocyte Differentiation. Endocrinology 148(4): 1539-1549. (Energy expenditure, mice, France) Cariou B (2007) FXR-deficiency confers increased susceptibility to torpor FEBS Letters, 581(27): 5191-5198. (Energy expenditure, mice, France, Netherlands) Clerc P et al. (2007) Involvement of Cholecystokinin 2 Receptor in Food Intake Regulation: Hyperphagia and Increased Fat Deposition in Cholecystokinin 2 Receptor-Deficient Mice. Endocrinology 48(3): 10391049. (Energy expenditure, mice, France) Ikeuchi M et al. (2007) Effects of Astaxanthin in Obese Mice Fed a High-Fat Diet. Bioscience, Biotechnology, and Biochemistry. 71(4): 893-899. (obesity, mice, Japan) Prieto-Lloret J et al. (2007) Hypoxia transduction by carotid body chemoreceptors in mice lacking dopamine D2 receptors. J. Appl. Physiol. 103: 1269-1275 (LE 400-4, mice, Spain) Tiraby C et al. (2007) Resistance to high-fat-diet-induced obesity and sexual dimorphism in the metabolic responses of transgenic mice with moderate uncoupling protein 3 overexpression in glycolytic skeletal muscles. Diabetologia. 50(10): 2190-2199. (Energy expenditure, mice, France) Valle A et al. (2007) Sex Differences in Brown Adipose Tissue Thermogenic Features During Caloric Restriction. Cell. Physiol. Biochem. 19:195-204. (Rat, Spain). Franckhauser S, Muñoz S, Elias I, Ferre T, Bosch F (2006) Adipose Overexpression of Phosphoenolpyruvate Carboxykinase Leads to High Susceptibility to Diet-Induced Insulin Resistance and Obesity. Diabetes 55:273-280. (Energy expenditure, mice, Spain) Bienvenu G, Seurin D, Le Bouc Y, Even P, Babajko S, Magnan D (2005) Dysregulation of energy homeostasis in mice overexpressing insulin-like growth factor-binding protein 6 in the brain. Diabetologia. 48(6): 1189-1197. (O2 consumption, mice, France) Prieto-Lloret J et al. (2003) Ventilatory responses and carotid body function in adult rats perinatally exposed to hyperoxia. J. Physiol. 154: 126-144 (LE 400-4, spirometry, rat, Spain)

Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

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Food & Drink/Metabolism

Metabolism Software and Associated Modules Metabolism Software METABOLISM software is the last element of the chain of components of the Panlab/Harvard Apparatus modular OXYLET system. METABOLISM allows the extraction of the data obtained from these Panlab/Harvard Apparatus devices as well as the calculation of important parameters for physiological studies. A combined evaluation of the respiration metabolism, food/drink intake, spontaneous activity and rearing is then rendered possible by the use of this very simple and easy-to-use software. METABOLISM consists in different modules, activated upon customer request:

software species is hardware specific

Key Features

➤ Converts and analyzes analog signals received from the different modules of our Oxylet System ➤ Calculates data in user-defined intervals of time

➤ Allows correlation between food/drink consumption, O2/CO2 metabolism and associated animal spontaneous activity

Parameters Measured ➤ O2 consumption

➤ CO2 production ➤ Respiratory quotient (O2/CO2) ➤ Energy Expenditure (using Weir equation)

META-OXY -> for O2/CO2 metabolism studies (Including treadmill based studies).

META-INT ->

META-ACT -> for Activity studies (Including rearing)

for Intake studies

The program gets data in digital form from the Panlab/Harvard Apparatus devices. METABOLISM can also import and convert analog data from the *.txt files generated by Data Acquisition Systems (PowerLab® recommended). Analog output from each of the software modules is intergrated and a graphical representation of the time course for each parameter is available. Evaluation curves allow an easy correlation between calorimetry, intake and activity. Gathered data can be processed and re-processed using different time intervals of calculation. The program displays a data table which can be saved in Excel format for further analysis.

Specifications Computer Requirements

3 GHz processor or higher (CELERON excluded; 4GHz recommended), 256 MB of RAM (512 MB recommended)

➤ Food consumption by user-defined interval of time

System Requirements

Windows® 98, 2000, XP or Vista compatible operating system (XP recommended)

➤ Mean activity by user-defined interval of time

Order # Model

Product

BH2 76-0080 METABOLISM

➤ Software CD

Metabolism Studies Plarform Needs Metabolism Experimental Modules for Calorimetry, Food & Drink Intake and/or Associated Activity and Rearing Respectively

BH2 76-0145 META-OXY

➤ Instruction manual

Metabolism Software Experimental Module Calorimetry (Respiratory Metabolism)

BH2 76-0081 META-INT

Metabolism Software Experimental Module Food & Drink Intake Monitoring

BH2 76-0087 META-ACT

Metabolism Software Experimental Module Activity and/or Rearing Recording

➤ Drink consumption by user-defined interval of time ➤ Number of rearing by user-defined interval of time

➤ Treadmill Data if applicable – speed, covered distance, number of shocks received, total duration of shocks received

Components Included ➤ Cables and connectors

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Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


Food & Drink/Metabolism PheCOMP System

Applications continued ➤ Meal Pattern Analysis ➤ Addiction ➤ Reward

➤ Obesity

➤ Alcohol Dependence ➤ Anxiety

Components Included ➤ Home cage ➤ Floor Grid

➤ Top lid with filter

➤ Platform including bridge amplifier, A/D converter, and data display

Options

➤ IR Frames for Activity and Rearing recording ➤ Wire bar lid for MultiTake

➤ Two-compartment separator

PheCOMP System Key Features

➤ Cutting-edge system for studying compulsive food and drink behavior in rodents ➤ Unmatched sensitivity for mice (20 mg)

➤ Pioneers in the use of very high stability weight transducers ➤ Multiple combinations of dispensers

➤ Ensures complete retrieving of food and liquid wastage ➤ Uncompromised access to food ➤ Continuous recording

➤ External dispensers preserving animal living space ➤ Compact system with minimal maintenance ➤ Enables place preference studies

Parameters Measured

➤ Food and drink intake amount (Compulse) ➤ Meal pattern analysis (Compulse) ➤ Global Activity (ActiTrack)

➤ Animal Tracking (ActiTrack)

Applications

➤ Food and Drink Intake

➤ Compulsive behavior tests – food/liquid preference, food/drink adulteration, anticipatory place preference

The PheCOMP system is an innovative solution for measuring food/liquid consumption and correlated motor activity as a means of assessing compulsive behavior in rodents. Developed as part of the EC-funded PHECOMP project (www.phecomp.com), this system allows for the behavioral characterization of several animal models of neuropsychiatric disorders related to compulsive behavior in a home cage environment. The Panlab/Harvard Apparatus PheCOMP system uses weight transducer technology for measuring food and drink consumption, thus allowing a continuous signal and precise analysis of animal meal pattern with our associated powerful software package. The animal home cage can be associated with up to four external units for food or drink, all user-defined. The system registers absorbed food and its wastage by means of weight transducers of very high stability mounted into the supporting platform under each cage. The volume of water consumed, along with any leakage, is also accounted for using the same transducers. Animal activity and rearing are recorded simultaneously using 2dimensional infrared frames. The signals from each weight transducer unit and the IR frame are amplified, digitalized and sent to the PheCOMP software for data acquisition and analysis. A track of the animal’s activity is recorded and can be analyzed using our ActiTrack software for further analysis of the animal’s position throughout the experiment. They system can be expanded easily with a single cable connecting the platforms in series and the last platform is connected by RS-232/USB to the PC.

➤ Global Activity

➤ Locomotor Activity ➤ Rearing

➤ Stereotypies

➤ Circadian Rhythms Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com

109


Food & Drink/Metabolism PheCOMP System (continued) The modular design of the PheCOMP system allows a wide range of experimental procedures for characterizing the evolution of animal compulsive behavior: •

General schedule for behavioral testing obese vs. non-obese animals

Choice test

Bitter test

Starvation

Screening of anti-obesity compounds

Specifications Accuracy

< 0.03 mg for both food and drink

Home Cage Dimensions

189 x 297 x 128 mm

Platform Dimensions

410 x 320 x 75 mm

Activity IR Frame

400 x 290 x 13 mm, 16 x 16 beams (16mm spaced)

Rearing IR Frame

400 x 16 mm, 16 x 16 beams (16 mm spaced)

Computer Requirements

Windows® 98, 2000, XP or Vista compatible system, 3 GHz Hard disk, 512 MB or RAM (1GM recommended), 256 color palette graphics card for 1024 x 768 pixels, 32 bit true color RGB display, one free RS-232 port or 1 free USB port

Order # Model

Product

BH2 76-0203 MultiTake

PheCOMP System Including Home Cage, Lid with Filter, Grid Floor, Bridge Amplifies, A/D Converter, RS-232 (USB), Data Display. Requires Combinations of LE1401 and LE1402

BH2 76-0204 Compulse

PheCOMP System Software

BH2 76-0209 LE1401

MultiTake Feeder for Mouse

BH2 76-0210 LE1402

MultiTake Drink Unit 150 ml for Mouse

BH2 76-0206 LE8827

MultiTake IR Frames for Activity/Rearing

BH2 76-0425 LE1403

MultiTake 2-Compartment Divider

BH2 76-0205 LE1404

MultiTake Home Cage Top Filter

BH2 76-0207 LE1405

MultiTake Grid Floor

BH2 76-0208 LE1406

MultiTake Wire Bar Lid

BH2 76-0003 ActiTrack

ActiTrack Software for Activity/Rearing

OPTIONS

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Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Panlab | Harvard Apparatus • Spain +34934190709 • International +34834750697 • fax +34934750699 • www.panlab.com


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