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

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 mug), directly into the medial nucleus accumbens shell dose-dependently attenuated drug seeking induced by 10 mg/kg cocaine. Microinjection of 1.0 mug 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.