Journal
PSYCHOPHARMACOLOGY
Volume 168, Issue 1-2, Pages 132-138Publisher
SPRINGER-VERLAG
DOI: 10.1007/s00213-002-1298-5
Keywords
reinstatement; nucleus accumbens; cocaine; dopamine; SCH-23390
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Funding
- NIDA NIH HHS [R01 DA12171, DA15263, F30 DA14205] Funding Source: Medline
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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.
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