This study examined the roles of the nucleus accumbens (NAc), medial prefrontal cortex, basolateral amygdala, and ventral subiculum of the hippocampus in the expression of Pavlovian conditioned hyperactivity responses to cocaine-related stimuli. This was accomplished by pharmacologically inhibiting these regions prior to drug-free tests for conditioned hyperactivity in an environment previously associated with cocaine. The results indicate that conditioned hyperactivity could be disrupted by infusions of the GABA-B agonist, baclofen (0.2 nmol/0.5 microl/side) into the NAc, or completely blocked by infusions of the GABA-A agonist, muscimol (0.1 and 0.2 nmol/0.5 microl/side) into the medial prefrontal cortex. In contrast, conditioned hyperactivity was unaffected by pharmacological inhibition of the basolateral amygdala, the ventral subiculum, or sites dorsal to the NAc or prefrontal cortex. These findings suggest that the NAc and the prefrontal cortex are crucial elements of the neural circuitry underlying the expression of Pavlovian conditioned responses to cocaine-related stimuli.