The habit-forming effects of abused drugs depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens (NAcc). To examine whether different NAcc subterritories (core and medial shell) exhibit a differential distribution of neurons showing phasic firing patterns correlated with drug-seeking behavior, rats were trained to self-administer cocaine, and activity of single NAcc neurons was recorded. In the presence of a discriminative-stimulus (S_D) tone, a single lever press produced an intravenous infusion of cocaine (0.35 mg/kg), terminated the tone, and started an inter-tone-interval ranging from 3 to 6 minutes. Lever presses during this inter-tone-interval had no programmed consequences. In addition to evaluating neuronal firing patterns associated with cocaine-reinforced presses, we also evaluated firing patterns associated with unreinforced lever presses to allow interpretation of firing free of factors other than the instrumental response (such as tone-off and onset of the pump signaling drug infusion). Core neurons exhibited a greater change in firing than medial shell neurons both in the seconds preceding the reinforced and unreinforced lever press response, and in the seconds following the unreinforced response. Core and medial shell neurons exhibited similar changes in firing during the seconds following the cocaine-reinforced press. The differential distribution of neurons exhibiting phasic changes in firing preceding the lever press suggests that the physiological activity of core neurons may play a greater role than that of medial shell neurons in processes related to the execution of conditioned drug-seeking responses.