Neurobiology Of Relapse To Opiate and Psychostimulant Drugs

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

High rates of relapse to drug use after prolonged drug-free periods characterize the behavior of people addicted to opioid and psychostimulant drugs. The behavioral and neurochemical events that contribute to these high relapse rates, however, are not well understood. Relapse can be induced in human subjects and laboratory animals by re-exposure to the drug previously used or re-exposure to environmental cues paired with drug self-administration. We are using different animal models of relapse to study brain systems and neurotransmitters involved in relapse induced by these stimuli in rats with a history of opioid (heroin, oxycodone, fentanyl) and psychostimulant (cocaine, methamphetamine) self-administration. In these studies, abstinence prior to relapse testing is achieved by either extinction of the drug-reinforced responding, homecage forced abstinence, or voluntary abstinence induced by adverse consequences of drug self-administration or giving rats a choice between the drug and appetitive non-drug reward like palatable food and positive social interaction with a peer. During the current reporting period (September 2024 to present), we published several papers, including studies on: (1) the roles of the claustrum and dorsomedial striatum in relapse to opioid seeking; (2) a dose-extending placebo effect in a rat model of buprenorphine maintenance; (3) a new method for assessing individual differences in addiction vulnerability and relapse using our lab’s social reward vs. heroin choice model; (4) the effect of a mixed nociceptin/mu-opioid receptor partial agonists on relapse to heroin seeking; and (5) a novel rat model of operant negative reinforcement in opioid-dependent rats. We also published a major review on the phenomenon of incubation of drug craving, the time-dependent increase in drug seeking during abstinence.