Contribution of the Ventral Tegmental Area to Cocaine-seeking Maintained by a Drug-paired Conditioned Stimulus in Rats

Stimuli paired with cocaine can maintain cocaine-seeking as conditioned reinforcers. Although converging evidence implicates a role for the ventral tegmental area (VTA) in the primary reinforcing effects of drugs of abuse, the role of the VTA in mediating associative influences over drug-seeking remains to be determined. The present study therefore investigated the contribution to CS-maintained cocaine-seeking under a second-order schedule of reinforcement of the VTA, and its terminal regions, the nucleus accumbens (NAcc) core and basolateral amygdala (BLA), previously shown to be critical for the acquisition of this behaviour. Inactivation of the VTA or NAcc core by direct infusion of a mixture of the GABA(A) and GABA(B) receptor agonists, baclofen and muscimol, decreased cocaine-seeking when rats were drug-free, while drug-seeking after self-administered cocaine was increased only when they were infused into the NAcc core. Inactivation of the BLA had no effect on drug-seeking. These results are discussed with reference to critical and distinct contributions of the VTA, NAcc core and BLA to drug-seeking maintained by conditioned reinforcers