Cholecystokinin antagonist lorglumide reverses chronic haloperidol-induced effects on dopamine neurons.

Intravenous administration of the cholecystokinin (CCK) antagonist lorglumide (LORG) reversed chronic haloperidol (CHAL)-induced depolarization inactivation (DI) of dopamine (DA) cells in both the A9 and A10 areas. Moreover, microinjection of LORG, but not naloxone, directly into the medial nucleus accumbens (mNAc) dose-dependently reversed CHAL-induced effect. LORG injected into other brain regions was without effect. These results suggest that CCK receptors in the mNAc form an important link for maintaining CHAL-induced DI of DA cells and that CCK is involved in the therapeutic action of antipsychotic drugs.