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.
BACKGROUND
A growing literature indicates that increased dopamine transmission in the nucleus accumbens contributes to priming-induced reinstatement of cocaine-seeking behavior.


OBJECTIVE
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.
Anderson
Sharon M
SM
Departments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA, USA.
Bari
Ausaf A
AA
Departments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA, USA.
Pierce
R Christopher
RC
Departments of Pharmacology and Psychiatry, Laboratory of Neuropsychopharmacology, Boston University School of Medicine, Boston, MA 02118, USA, USA. rcpierce@acs.bu.edu.|Department of Pharmacology, R-612, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA, USA. rcpierce@acs.bu.edu.
D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000523:psychology; D001552:Benzazepines / Q000008:administration & dosage*; D003042:Cocaine / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D003042:Cocaine