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

Int J Neuropsychopharmacol. 2009 Apr;12(3):431-6. doi: 10.1017/S1461145709000054. Epub 2009 Feb 23.


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) D(1) 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 D(1) receptor antagonist, SCH 23390 (0.02-2.0 microg/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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 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


  • Benzazepines
  • Narcotics
  • Receptors, Dopamine D1
  • SCH 23390
  • Heroin