Inhibition of climbing and mossy fiber input to mouse cerebellar Purkinje cells by cholecystokinin

Abstract

Cholecystokinin (CCK)-8S was found both to decrease basal and to antagonize harmaline-dependent increases in cerebellar cyclic GMP (cGMP) in the mouse. These actions were not blocked by parenteral pretreatment with naloxone, proglumide or CR-1409, indicating a central-type CCK receptor activation with no involvement of opioid systems. These data were further confirmed by the greater potency (200x) of intraventricular relative to s.c. doses for CCK-8S. The intraventricular administration of CCK-4, t.BOC.CCK-4 and CCK-8US also resulted in decreased cerebellar cGMP levels, consistent with a central-type CCK receptor action. Direct administration of CCK-8S into the cerebellum failed to alter either basal or harmaline-stimulated cerebellar cGMP levels, indicating that the actions of this peptide on cerebellar cGMP are not directly at the level of the cerebellum. The convulsants, picrotoxin and pentylenetetrazol, elevated cerebellar cGMP with no antagonism by pretreatment with s.c. CCK-8S. In marked contrast, the increases in cerebellar cGMP induced by treatment with amphetamine, apomorphine, DN 1417, oxotremorine and harmaline were all antagonized by pretreatment with s.c. CCK-8S. These data are consistent with CCK receptor involvement in the regulation of climbing and mossy fiber input to the cerebellum. These actions apparently involve the central-type CCK receptor that resides outside of the cerebellum proper. The exact site(s) of action for CCK-8S remain(s) to be defined.