Rationale: When people with drug addiction encounter cues associated with drug use, this can trigger cravings and relapse. These cues can include conditioned stimuli (CSs) signaling drug delivery and discriminative stimuli (DSs) signaling drug availability. Compared to CS effects, DS effects are less explored in preclinical studies on cue-induced relapse.
Objective: We compared CS and DS effects on reward seeking following abstinence from intermittent-access cocaine (or sucrose) self-administration.
Methods: During 15-20 intermittent-access sessions, rats self-administered i.v. cocaine or sucrose pellets paired with a light-tone CS. Cocaine/sucrose was available for 5-min (signalled by a light; DS+) and unavailable for 25 min (signalled by different lighting conditions; DS-), and this cycled for 4 h/session. Following abstinence, we measured cocaine/sucrose seeking under extinction triggered by CS and DS presentation, and instrumental responding reinforced by these cues.
Results: Across intermittent-access sessions, rats increased lever pressing for cocaine or sucrose during DS+ periods and decreased responding during DS- periods. On days 2 and 21 of abstinence, only presentation of the DS+ or DS+ and CS combined elicited increased cocaine/sucrose-seeking behaviour (i.e., increased active lever presses). Presenting the DS- alongside the DS+ suppressed the increased cocaine-seeking behaviour otherwise produced by the DS+ . Finally, on day 21 of abstinence, rats showed equivalent levels of lever pressing reinforced by the DS+ , CS and by the DS+ and CS combined, suggesting comparable conditioned reinforcing value.
Conclusions: After intermittent self-administration, cocaine-associated DSs and CSs acquire similar conditioned reinforcing properties, but DSs more effectively trigger increases in drug seeking.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00213-024-06614-9 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
L-type calcium channel blockade attenuates the anxiogenic-like and pro-depressive-like effects of cocaine abstinence in female and male rats.
Neuroscience
January 2025
Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; Wu Tsai Institute, Yale University, New Haven, CT, USA; Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA. Electronic address:
Cocaine abstinence and withdrawal are linked to relapse, heightened anxiety, and depressive-like symptoms. While L-type calcium channels (LTCCs) have been associated with cocaine use disorders in humans and drug-seeking behavior in rodent models, their role in mood-related symptoms during cocaine abstinence remains unclear. This study examined whether blocking LTCCs with isradipine could alter anxiety and depressive symptoms induced by cocaine abstinence.
View Article and Find Full Text PDFSeeking under threat of adversity: assessing control over reward pursuit in rats.
Psychopharmacology (Berl)
December 2024
Department of Population Health Sciences, Unit of Animals in Science and Society, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Rationale: Substance use disorder (SUD) is a chronic relapsing brain disorder that is characterised by loss of control over substance use. A variety of rodent models employing punishment setups have been developed to assess loss of control over substance use, i.e.
View Article and Find Full Text PDFThe function of the ZFP189 transcription factor in the nucleus accumbens facilitates cocaine-specific transcriptional and behavioral adaptations.
Mol Psychiatry
November 2024
Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Distinguishing the brain mechanisms affected by distinct addictive drugs may inform targeted therapies against specific substance use disorders (SUDs). Here, we explore the function of a drug-associated, transcriptionally repressive transcription factor (TF), ZFP189, whose expression in the nucleus accumbens (NAc) facilitates cocaine-induced molecular and behavioral adaptations. To uncover the necessity of ZFP189-mediated transcriptional control in driving cocaine-induced behaviors, we created synthetic ZFP189 TFs of distinct transcriptional function, including ZFP189, which activates the expression of target genes and exerts opposite transcriptional control to the endogenously repressive ZFP189.
View Article and Find Full Text PDFBackground: Repeated cocaine use produces neuroadaptations that support drug craving and relapse in substance use disorders (SUDs). Powerful associations formed with drug-use environments can promote a return to active drug use in SUD patients, but the molecular mechanisms that control the formation of these prepotent drug-context associations remain unclear.
Methods: In the rat intravenous cocaine self-administration (SA) model, we examined the role and regulation of histone deacetylase 5 (HDAC5) in the prelimbic (PrL) and infralimbic (IL) cortices in context-associated drug seeking.
Cannabidiol or ketamine for preventing the impact of adolescent early drug initiation on voluntary ethanol consumption in adulthood.
Front Pharmacol
August 2024
University Research Institute of Health Sciences, University of the Balearic Islands, Palma, Spain.
Background: Few studies have previously evaluated the long-term impact of initiating the combined use of alcohol and cocaine early-in-life during adolescence. Our preclinical study characterized changes in affective-like behavior and/or voluntary ethanol consumption emerging later on in adulthood induced by a prior adolescent drug exposure, as well as tested therapeutical interventions (i.e.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!