Animal Models of Drug Relapse and Craving after Voluntary Abstinence: A ReviewShow others and affiliations
2021 (English)In: Pharmacological Reviews, ISSN 0031-6997, E-ISSN 1521-0081, Vol. 73, no 3, p. 1050-1083Article, review/survey (Refereed) Published
Abstract [en]
Relapse to drug use during abstinence is a defining feature of addiction. During the last several decades, this clinical scenario has been studied at the preclinical level using classic relapse/reinstatement models in which drug seeking is assessed after experimenter-imposed home-cage forced abstinence or extinction of the drug-reinforced responding in the self-administration chambers. To date, however, results from studies using rat relapse/reinstatement models have yet to result in Food and Drug Administration-approved medications for relapse prevention. The reasons for this state of affairs are complex and multifaceted, but one potential reason is that, in humans, abstinence is often self-imposed or voluntary and occurs either because the negative consequences of drug use outweigh the drugs rewarding effects or because of the availability of nondrug alternative rewards that are chosen over the drug. Based on these considerations, we and others have recently developed rat models of relapse after voluntary abstinence, achieved either by introducing adverse consequences to drug taking (punishment) or seeking (electric barrier) or by providing mutually exclusive choices between the self-administered drug and nondrug rewards (palatable food or social interaction). In this review, we provide an overview of these translationally relevant relapse models and discuss recent neuropharmacological findings from studies using these models. We also discuss sex as a biological variable, future directions, and clinical implications of results from relapse studies using voluntary abstinence models. Our main conclusion is that the neuropharmacological mechanisms controlling relapse to drug seeking after voluntary abstinence are often different from the mechanisms controlling relapse after home-cage forced abstinence or reinstatement after extinction. Significance Statement-This review describes recently developed rat models of relapse after voluntary abstinence, achieved either by introducing adverse consequences to drug taking or seeking or by providing mutually exclusive choices between the self-administered drug and nondrug rewards. This review discusses recent neuropharmacological findings from studies using these models and discusses future directions and clinical implications.
Place, publisher, year, edition, pages
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS , 2021. Vol. 73, no 3, p. 1050-1083
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-181041DOI: 10.1124/pharmrev.120.000191ISI: 000708960700007PubMedID: 34257149OAI: oai:DiVA.org:liu-181041DiVA, id: diva2:1611939
Note
Funding Agencies|Intramural Research Program of National Institutes of Health National Institute on Drug Abuse (NIDA) [1ZIADA000434-20]; Swedish Research Council International postdoctoral grant [2019-00658]; NIDAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA047976]; National Institute of General Medical Sciences Postdoctoral Research Associate Grant [1F12GM128603]
2021-11-162021-11-162021-11-16