Nucleus accumbens shell and core involvement in drug context-induced reinstatement of cocaine seeking in rats

Rationale The nucleus accumbens (NAC) is a functionally heterogeneous brain region with respect to its involvement in cocaine-seeking behavior triggered by drug-associated explicit conditioned stimuli, foot shock stress, or cocaine itself in the reinstatement animal model of drug relapse. However, it is not known whether the NAC or its subregions are critical for reinstatement of cocaine-seeking behavior produced by re-exposure to a previously cocaine-paired environmental context. Objectives The present study was designed to evaluate potentially unique contributions of the NAC core and shell to this behavior. Materials and methods Rats were trained to lever press for unsignaled cocaine infusions (0.15 mg/infusion, intravenous) in a distinct environmental context. Lever responding was then extinguished in a distinctly different environmental context (extinction context) during a minimum of seven daily training sessions. Subsequently, using a counterbalanced testing design, rats were re-exposed to the cocaine-paired context or the extinction context while cocaine seeking (i.e., responding on the previously cocaine-reinforced lever) was assessed. Before each test session, neural activity was inhibited selectively in the NAC core or shell using bilateral microinfusions of the γ-aminobutyric acid agonists, baclofen and muscimol (0/0 or 1.0/0.1 mM; 0.3 μl per hemisphere). Results Neural inactivation of the NAC shell or core attenuated responding in the cocaine context and, interestingly, increased responding in the extinction context. Control experiments indicated no effects on general activity or food-reinforced instrumental behavior. Conclusions These findings suggest that both subregions of the NAC may promote context-induced reinstatement by facilitating drug context-induced motivation for cocaine and context discrimination.