Electrophysiological recording procedures were used to examine the responsiveness of nucleus accumbens (Acb) neurons to stimuli associated with cocaine delivery during a multiple schedule for water reinforcement and cocaine self-administration. Rats (n=9) were trained to press one lever for water reinforcement (0.05 ml/resp.; fixed ratio 1; FR1; 15 min) and a second spatially distinct lever for intravenous cocaine (0.33 mg/infusion; FR1; 2 h). The delivery of each reinforcer was signaled by different auditory stimuli. Of 101 neurons, 52 cells were classified as phasically active, exhibiting one of four well-defined types of patterned discharges relative to the water- or cocaine-reinforced response [J. Neurosci., 14(12) (1994) 7735; J. Neurosci., 20(11) (2000) 4255]. Acb cells were examined in test sessions consisting of 'probe' trials during which the stimulus previously paired with cocaine infusion was randomly presented in a response-independent manner during the self-administration portion of the session. Results showed that only neurons that exhibited changes in firing rate within seconds following the reinforced response for cocaine (but not water) were activated by the stimulus. This finding indicates that the responsiveness of cocaine selective neurons to cocaine-associated stimuli likely represents a conditioned response as opposed to a generalized stimulus-evoked discharge.