Cholecystokinin (CCK) and dopamine (DA) coexist in a subpopulation of neurons of the ventral tegmental area projecting to the nucleus accumbens. The present experiments were undertaken to determine the effect of acute and long-term administration of haloperidol on the responsiveness of accumbens neurons to microiontophoretic applications of the sulfated cholecystokinin octapeptide (CCK-8S), kainate (KA), and DA and on the density of CCK, D1, and D2 receptors determined by radioautography. Acute administration of haloperidol (1 mg/kg, i.v.) did not modify the neuronal responsiveness to DA and KA but increased that to CCK-8S. Long-term treatment with haloperidol decanoate (4 mg/kg/week, i.m., for 3–5 weeks) induced a marked increase in the responsiveness to CCK-8S, without noticeable change of that to DA and KA. After a 5 week treatment, significant increases in the amounts of CCK and D2 binding were found in the nucleus accumbens, whereas D1 binding parameters remained unchanged. Since long-term haloperidol treatment results in a depolarization inactivation of A10 dopaminergic neurons, these results suggest that, despite the reduced firing activity of mesolimbic dopaminergic neurons induced by the long-term haloperidol treatment, dopamine is still released in an amount sufficient to maintain a normal neuronal responsiveness of postsynaptic accumbens neurons to DA, whereas the release of CCK is possibly decreased to a greater extent, resulting in an enhanced responsiveness of the neurons to this peptide.