Cholecystokinin attenuates basal and drug-induced increases of limbic and striatal dopamine release

Subcutaneous administration to mice of the sulfated octapeptide of cholecystokinin (CCK; 0.2-1 mg/kg) lowered dopamine release and metabolism in the caudate-putamen and frontal cortex in a dose- and time-related manner. Twelve-fold higher doses of CCK were required to lower dopamine release and metabolism in the olfactory tubercle. Amphetamine-induced increases in dopamine release but not metabolism in the caudate-putamen and olfactory tubercle were attenuated in a dose-related manner by CCK. Increases in dopamine release and metabolism following haloperidol were also attenuated by CCK. These data are consistent with the potential antipsychotic action of CCK receptor agonists. CCK appears to be a suppressor of striatal, limbic and cortical dopamine release, especially when release is augmented.