When CCK-8 was injected in the rat posterior nucleus accumbens, where it is in part co-localized with dopamine, a decrease in exploration of the four hole box and the elevated plus maze was observed. In this study, a selective destruction of the dopaminergic mesoaccumbens pathway induced by local injection of 6-hydroxydopamine (6-OHDA) in the nucleus accumbens was found to suppress the CCK-8-evoked behavioral effects. Moreover, an ex vivo measurement of the dopaminergic metabolism has been performed after injection of CCK-8 in the posterior nucleus accumbens by electrochemical detection of dopamine and its metabolites extracted from punches of brain tissue. The results showed that CCK-8 decreased the turnover of dopamine in the posterior part but not in the anterior part of the nucleus accumbens or in the ventral tegmental area. Furthermore, sulpiride, a selective antagonist for D2 dopamine receptors, but not SCH 23390, a selective antagonist for D1 dopamine receptors, prevented CCK-8-induced behavioral responses. Taken together, these results suggest that CCK-8 could be involved in behavioral adaptation to situations producing change in emotional and/or motivational states through modulation of presynaptic D2 receptor functioning.