Dopamine D1 receptor antagonism in the prelimbic cortex blocks the reinstatement of heroin-seeking in an animal model of relapse

• Published in: The international journal of neuropsychopharmacology Vol. 12; no. 3; pp. 431 - 436
• Main Author: See, Ronald E.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.04.2009; Oxford University Press
• Subjects: Analysis of Variance; Animals; Behavior, Addictive - drug therapy; Behavior, Addictive - pathology; Behavior, Addictive - psychology; Benzazepines - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Heroin - administration & dosage; Limbic System - drug effects; Male; Motor Activity - drug effects; Narcotics - administration & dosage; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - antagonists & inhibitors; Reinforcement (Psychology); Dopamine; heroin; reinstatement; relapse; prelimbic
• ISSN: 1461-1457; 1469-5111
• DOI: 10.1017/S1461145709000054

In brain regions that have been implicated in the reinstatement of drug-seeking, the prelimbic cortex has emerged as a critical regulator of relapse behaviours. Here, the effects of prelimbic cortex dopamine (DA) D1 receptor antagonism on drug-seeking produced by heroin-paired cues, or by a single priming dose of heroin are examined. Rats lever-pressed daily for i.v. heroin discretely paired with a conditioned stimulus during 3-h sessions for a period of 2 wk, followed by extinction and reinstatement of drug-seeking by previously heroin-paired cues (tone+light) or heroin-priming injections (0.25 mg/kg) in the absence of heroin reinforcement. Intracranial infusion of the DA D1 receptor antagonist, SCH 23390 (0.02–2.0 μg/side), into the prelimbic cortex potently and dose dependently attenuated heroin-seeking in response to either cue presentations or a priming dose of heroin. These results suggest that DA D1 receptors regulate prefrontal cortex pathways necessary for the reinstatement of heroin-seeking.