Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism

• Published in: Drug and alcohol dependence Vol. 187; pp. 327 - 334
• Main Authors: Ball, Kevin T., Stone, Eric, Best, Olivia, Collins, Tyler, Edson, Hunter, Hagan, Erin, Nardini, Salvatore, Neuciler, Phelan, Smolinsky, Michael, Tosh, Lindsay, Woodlen, Kristin
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-06-2018; Elsevier Science Ltd
• Subjects: Abstinence; Addictions; Animal models; Animals; Benzazepines - administration & dosage; Cocaine; Cocaine - administration & dosage; Cocaine-Related Disorders - psychology; Cues; Disease Models, Animal; Dopamine; Dopamine Antagonists - administration & dosage; Dopamine D1 receptors; Drug abuse; Drug addiction; Drug self-administration; Drug withdrawal; Drug-Seeking Behavior - drug effects; Extinction; Extinction, Psychological - drug effects; Hostility; Induced; Male; Management; Narcotics; Occupational stress; Priming; Psychological extinction; Rats; Rats, Sprague-Dawley; Receptors; Receptors, Dopamine D1 - antagonists & inhibitors; Reinstatement; Relapse; Repetition Priming - drug effects; Restraint, Physical - psychology; Self Administration; Stress; Stress, Psychological - psychology; Stresses; Vulnerability; Withdrawal; CS; mPFC; Relapse; IL; Dopamine; D1R; Reinstatement; Cocaine; FR; Abstinence; Stress; MDMA
• DOI: 10.1016/j.drugalcdep.2018.03.024
• EISSN: 1879-0046
• ISSN: 0376-8716

•The effect of chronic restraint stress on subsequent cocaine seeking was tested.•Both extinction- and abstinence-based animal relapse models were used.•Chronic restraint stress caused increase in cocaine priming-induced reinstatement.•A dopamine D1-like receptor antagonist, combined with stress, attenuated this effect.•Prior antagonist treatment resulted in increased cue-induced reinstatement.
A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers.
We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models. Rats were trained to press a lever for I.V. cocaine infusions (0.50 mg/kg/infusion) paired with a discrete tone + light cue in daily 3-h sessions. Following self-administration, rats were exposed to a chronic restraint stress procedure (3 h/day) or control procedure (unstressed) during the first seven days of a 13-day extinction period during which lever presses had no programmed consequences. This was followed by cue- and cocaine priming-induced drug seeking tests. In a separate group of rats, cocaine seeking was assessed during forced abstinence both before and after the same chronic stress procedure.
A history of chronic restraint stress was associated with increased cocaine priming-induced drug seeking, an effect attenuated by co-administration of SCH-23390 (10.0 μg/kg; i.p.), a dopamine D1-like receptor antagonist, with daily restraint. Repeated SCH-23390 administration but not stress during extinction increased cue-induced reinstatement.
Exposure to chronic stress during early withdrawal may confer lasting vulnerability to some types of relapse, and dopamine D1-like receptors appear to mediate both chronic stress effects on cocaine seeking and extinction of cocaine seeking.