Sharon M Anderson1, Ausaf A Bari1, R Christopher Pierce2,3. 1. Departments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA, USA. 2. Departments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA, USA. rcpierce@acs.bu.edu. 3. Department of Pharmacology, R-612, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA, USA. rcpierce@acs.bu.edu.
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 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.
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.
Authors: Leonardo A Guercio; Mackenzie E Hofmann; Sarah E Swinford-Jackson; Julia S Sigman; Mathieu E Wimmer; Mark L Dell'Acqua; Heath D Schmidt; R Christopher Pierce Journal: Neuropsychopharmacology Date: 2017-12-12 Impact factor: 7.853