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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

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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.

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Acknowledgements.

The authors thank Audrey Pierce for technical and administrative assistance as well as comments on an earlier version of this manuscript. This research was supported by a grant from the National Institutes of Health (RO1 DA12171). R.C.P. also was supported by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award and a New Investigator Award from the Harcourt General Charitable Foundation. S.M.A. and A.A.B. were partially supported by National Research Service Awards from the National Institutes Health (F31 DA15263 and F30 DA14205, respectively).

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Authors and Affiliations

  1. Departments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA, USA

    Sharon M. Anderson, Ausaf A. Bari & R. Christopher Pierce

  2. Department of Pharmacology, R-612, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA, USA

    R. Christopher Pierce

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  1. Sharon M. Anderson
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  2. Ausaf A. Bari
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Correspondence to R. Christopher Pierce.

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Anderson, S.M., Bari, A.A. & Pierce, R.C. 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 168, 132–138 (2003). https://doi.org/10.1007/s00213-002-1298-5

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  • DOI: https://doi.org/10.1007/s00213-002-1298-5

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