Cholecystokinin-induced inhibition of dopamine neurotransmission: comparison with chronic haloperidol treatment.

A dose-dependent inhibition of DA release was observed by in vivo electrochemical techniques after acute i.v. injections of CCK8-S (1.0-8.0 micrograms/kg). The threshold dose was 1.0 microgram/kg, and maximum inhibition of release (90%) was obtained with doses of 4 and 8 micrograms/kg. Injections of CCK8-US (4-20 micrograms/kg) had no effect on DA release. Repeated treatment with haloperidol (0.5 mg/kg s.c.) for 21 days produced a 47% inhibition of DA release in the nucleus accumbens. Apomorphine (50 micrograms/kg) reversed the inhibitory effects of both acute injections of CCK8-S and prolonged haloperidol treatment on DA release. In contrast, apomorphine (50 micrograms/kg) administered alone inhibited DA release, presumably via hyperpolarization of DA neurons. The attenuation of DA release by either an acute injection of CCK8-S or repeated treatment with haloperidol is attributed to the induction of depolarization block in mesolimbic DA neurons. These data may be indicative of antipsychotic properties of CCK8-S.