Sulfated cholecystokinin octapeptide (CCK-8S) has been reported to be extensively colocalized with dopamine in the posterior, but not the anterior, portion of the nucleus accumbens (NAc). The hypothesis tested in the present study was that CCK-8S alters the release of dopamine in this structure and the actions it produces are dependent on the extent of colocalization with dopamine. We observed in vitro that CCK-8S enhanced the resting release of dopamine from the posterior, but not anterior, NAc. It was also found that CCK-8S attenuated the release of dopamine induced by potassium-evoked depolarization in both regions of the NAc, although the concentration-release curves for the two areas differed. In the posterior NAc, a biphasic response was seen whereas, in the anterior NAc, there was a monophasic attenuation. Proglumide, a putative CCK-8S antagonist, was found to antagonize the action of a low concentration of CCK-8S on 40 mM K+-induced dopamine release from slices of the posterior, but not anterior, NAc. Unsulfated CCK-8 had mixed action on K+-evoked dopamine release, as it enhanced this form of release in the posterior NAc but attenuated it in the anterior NAc. Additionally, we found no effect of sulpiride on the actions of CCK-8S with respect to evoked release, suggesting that CCK-8S is not acting to alter dopamine autoreceptor function, as has recently been hypothesized. In summary, our results demonstrate that the observed effects of CCK-8S on dopamine release are dependent upon the region of the NAc studied, and there appear to be different subtypes of CCK-8S receptors present in the two regions.