Administration of the D1-like dopamine receptor antagonist SCH-23390 into the medial nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug-seeking behavior in rats

Psychopharmacology (Berl). 2003 Jul;168(1-2):132-138. doi: 10.1007/s00213-002-1298-5. Epub 2002 Dec 19.


Rationale: A growing literature indicates that increased dopamine transmission in the nucleus accumbens contributes to priming-induced reinstatement of cocaine-seeking behavior.

Objectives: The present experiments were designed to assess the role of D(1)-like dopamine receptors in the nucleus accumbens core and shell subregions in cocaine priming-induced reinstatement of drug seeking.

Methods: Rats were trained to lever press for cocaine using a fixed ratio (FR) 5 schedule of reinforcement. Drug-seeking was measured by active lever presses during daily 2-h sessions. After approximately 30 days of cocaine self-administration, the animals underwent an extinction phase during which cocaine was replaced with saline. Daily extinction sessions were conducted until responding was consistently less than 10% of the response rate maintained by cocaine self-administration. After the extinction phase, priming-induced reinstatement of cocaine-seeking behavior was assessed.

Results: Cocaine dose-dependently reinstated cocaine seeking, with robust drug seeking at 10 mg/kg cocaine. Administration of the D(1)-like dopamine receptor antagonist, SCH-23390 (0.1-1.0 micro g), directly into the medial nucleus accumbens shell dose-dependently attenuated drug seeking induced by 10 mg/kg cocaine. Microinjection of 1.0 micro g SCH-23390 into either the nucleus accumbens core or lateral septum had no influence on cocaine-seeking behavior.

Conclusions: These results indicate that stimulation of D(1)-like dopamine receptors in the medial nucleus accumbens shell contributes to drug-induced reinstatement of cocaine-seeking behavior.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Addictive / drug therapy*
  • Behavior, Addictive / psychology
  • Benzazepines / administration & dosage*
  • Cocaine / administration & dosage*
  • Dopamine Antagonists / administration & dosage*
  • Dose-Response Relationship, Drug
  • Male
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / physiology


  • Benzazepines
  • Dopamine Antagonists
  • Receptors, Dopamine D1
  • Cocaine