Centrally administered CCK-8 suppresses activity in mice by a "peripheral-type" CCK receptor

Cholecystokinin octapeptide (CCK-8) administered either systemically (IP) or centrally (ICV) suppresses several types of behavior in mice including exploratory locomotion, rearing and grooming. At doses equimolar to those active for CCK-8, neither desulfated CCK-8 (CCK-8-DS), nor the protected C-terminus tetrapeptide fragment, BOC-CCK-4, is behaviorally active when administered either centrally or systemically. A potent and selective antagonist to the peripheral type (Type A) CCK receptor, A-65186, when given systemically, blocked the effects of systemically administered CCK-8, but failed to block the effects of ICV administered CCK-8. Central administration of A-65186 blocked the effects of ICV administered CCK-8. These results demonstrate that administration of exogenous CCK-8 to mice can suppress exploratory locomotion by acting either centrally or peripherally and that in either case the demonstrated behavioral effects are mediated via a "peripheral" type (Type A) CCK receptor.