RESEARCH
THE MEMORY TRACE OF ADDICTION: HOW DRUGLINKED MEMORIES IMPACT EMOTIONALITY AND DRUG-SEEKING IN AN EXPERIMENTAL MODEL OF OPIOID ABUSE Raena E. Greenbaum, Steven J. Simmons, William R. Haury, Amelia J. Eisch
Children’s Hospital of Philadelphia Research Institute; Abramson Pediatric Research Center; 3615 Civic Center Boulevard; Philadelphia, PA, USA.
ABSTRACT While efforts have been made to interpret the emotional effects of drug-taking and drug-seeking in humans, there is currently a gap in research on these affective changes in animal models for opioid use disorders (OUDs). Indeed, one way to measure emotional changes in a model of OUD is to study ultrasonic vocalizations (USVs) from the drug-taking rat, as two main frequency ranges are interpreted to reflect positive (50-kHz) and negative (22-kHz) affect. While used in studies on other drugs of abuse like cocaine, this study is the first to use USVs as a measure in the self-administration of a prescription opioid and during recall of drug-linked memories. We put rats (n=66) through intravenous self-administration of the prescription opioid oxycodone by training them to press a lever for intravenous drug infusions during behavioral sessions. This was followed by an extinction of the drug-taking behavior in either the drug-linked context or a novel context. This paper examines the results of two studies. The first was an analysis of emotionality over the course of the acquisition phase, which involved recording drug infusions earned, lever presses made, and USVs emitted by self-administering rats to characterize affective states associated with the development of addiction. We found that rats will experience greater negative affect early in acquisition, and greater positive affect in later acquisition sessions, and that a positive anticipatory affect will be experienced when the rats are exposed to the drug-paired context before the start of the session commences. The second study involved recording USVs emitted by rats during one single extinction probe test with different levels of drug-memory linkage to assess whether context and new action-outcome learning impact emotionality. The analysis of this extinction data is in progress, results of which hold important insights for understanding the neurobiology of drug-linked memory retrieval.
INTRODUCTION
experiences typified in opioid addiction, preventing such dependence has proven to be a serious clinical There has been a sharp increase in the prescription challenge and is an important research focus in the rate of opioids due to their unmatched capability to face of the current epidemic. relieve pain. However, their highly addictive qualities have led to severe consequences that have proven When patients were given a list of prescription opidifficult to address. Roughly 21-29% of patients pre- oids and asked to identify the one most desirable to scribed opioids for pain have reported misusing them themselves, the one most desirable among drug-using (SAMHSA 2017), and 75% of heroin users reported communities, and the one they deemed most addicthat their first opioid was a prescription drug (Cicero tive, oxycodone was ranked most highly in all catet al. 2014). Each day over 130 people in the Unit- egories (Remillard et al. 2019). Due to its immense ed States die due to overdose on opioids (SAMHSA “likability” in users, oxycodone has one of the highest 2017) and as of October 16, 2017, the United States potentials for abuse and dependence compared with government declared the opioid epidemic a public other prescription opioids. Subjective effects of the health emergency. high of a drug like oxycodone may contribute to the extent to which the drug is sought after initial use and It is clear that people do not take prescription opioids thus informs measures such as proclivity to opioid with the intention to become dependent; rather, the abuse as well as relapse propensity. Because relapse effect of the drugs includes intense emotional experi- is one of the main challenges in combating addiction, ences that are craved after the high wanes. Because an important next step in research is to understand much is still unknown about the dynamic subjective the subjective effects of prescription opioid use. 42 PENNSCIENCE JOURNAL | Spring 2022
