Cholecystokinin receptor subtypes and neuromodulation.

The sulfated octapeptide of cholecystokinin (CCK-8S) and CCK fragments have been administered to mice to determine the subtype and location of the CCK receptor that modulates the release of dopamine (DA) in brain. 1. Centrally (i.c.v.) or peripherally (s.c.) administered CCK-8S lowers DA release, and to a lesser extent, metabolism, in the neostriatum and olfactory tubercle. 2. DA release is decreased when the CCK-B selective compounds, unsulfated CCK-8 (CCK-8U) or the butoxycarbonyl tetrapeptide of CCK (t-boc-CCK-4), are given i.c.v. but not when injected s.c. 3. The increase in DA release following amphetamine administration is attenuated by i.c.v. but not s.c. injections of t-boc-CCK-4 or CCK-8U and by CCK-8S given via either route. 4. None of the s.c. actions of CCK-8S are prevented by the CCK-A receptor antagonist, L 364,718. CCK-B receptors in brain mediate the suppression by CCK of basal and augmented DA release. CCK-B receptor agonists may be useful for the treatment of psychiatric conditions that result from excessive DA release.