Administration of the D2 dopamine receptor antagonist sulpiride into the shell, but not the core, of the nucleus accumbens attenuates cocaine priming-induced reinstatement of drug seeking.
Enhanced dopamine transmission in the nucleus accumbens plays an important role in cocaine priming-induced reinstatement of drug-seeking behavior. However, the contribution of each dopamine receptor subtype to this behavior remains unclear. The present experiments were designed to assess the role of D2-like dopamine receptors in the nucleus accumbens core and shell subregions in cocaine priming-induced reinstatement of drug seeking. Rats were trained to lever press for cocaine using a fixed ratio (FR) 5 schedule of reinforcement. After approximately 18 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 less than 10% of the response rate maintained by cocaine self-administration. Following the extinction phase, priming-induced reinstatement of cocaine-seeking behavior was assessed. A range of doses of antagonists selective for D2- (sulpiride, 0.2 or 2.0 microg), D3- (U99194A, 3.9 or 7.8 microg), or D4- (L-750,667, 5.5 or 11 microg) dopamine receptors were microinjected into either the nucleus accumbens core, shell or lateral septum prior to a priming injection of cocaine (10 mg/kg, i.p.). Following administration into the shell, but not core or lateral septum, sulpiride dose-dependently attenuated reinstatement induced by a cocaine priming injection. In contrast, U99194A and L-750,667 failed to influence cocaine seeking at any of the doses tested in either accumbal subregion. Collectively, these findings indicate that activation of D2 dopamine receptors mediates cocaine priming-induced reinstatement of cocaine seeking in a region-specific manner within the nucleus accumbens.
Anderson
Sharon M
SM
Department of Pharmacology, Boston University School of Medicine, Boston, MA 02118, USA.
Schmidt
Heath D
HD
Pierce
R Christopher
RC
D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005108:Extinction, Psychological / Q000187:drug effects; D007189:Indans / Q000494:pharmacology; D008297:Male; D008845:Microinjections / Q000379:methods; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration; D013469:Sulpiride / Q000494:pharmacology*
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D007189:Indans; C103081:L 750667; D011725:Pyridines; D011758:Pyrroles; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; D013469:Sulpiride; D003042:Cocaine