Original Investigation

Psychopharmacology

, Volume 168, Issue 1, pp 132-138

First online:

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

  • Sharon M. AndersonAffiliated withDepartments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA
  • , Ausaf A. BariAffiliated withDepartments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA
  • , R. Christopher PierceAffiliated withDepartments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USADepartment of Pharmacology, R-612, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA Email author 

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Abstract

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 D1-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 D1-like dopamine receptor antagonist, SCH-23390 (0.1–1.0 µg), directly into the medial nucleus accumbens shell dose-dependently attenuated drug seeking induced by 10 mg/kg cocaine. Microinjection of 1.0 µg 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 D1-like dopamine receptors in the medial nucleus accumbens shell contributes to drug-induced reinstatement of cocaine-seeking behavior.

Keywords.

Reinstatement Nucleus accumbens Cocaine Dopamine SCH-23390