The CCK-A receptor antagonist devazepide but not the CCK-B receptor antagonist L-365,260 reverses the effects of chronic clozapine and haloperidol on midbrain dopamine neurons.

In this study, we examined the effects of the cholecystokinin-A (CCK-A) antagonist devazepide (MK 329) and the CCK-B antagonist L-365,260 to reverse the decrease in the number of spontaneously active dopamine (DA) cells in the ventral tegmental area and substantia nigra pars compacta after chronic haloperidol (HAL) or clozapine (CLOZ) treatment. The intravenous administration of devazepide (2 micrograms/kg) but not L-365,260 (2 micrograms/kg) reversed the reduction in the number of spontaneously active A9 and A10 DA cells produced by chronic HAL. Furthermore, devazepide also reversed the decrease in the number of spontaneously active A10 DA cells produced by chronic CLOZ administration. Overall, these results suggest that CCK-A but not CCK-B receptors play an important role in mediating or maintaining the chronic antipsychotic drug-induced effect on midbrain DA cells.