Hypolocomotion induced by peripheral or central injection of CCK in the mouse is blocked by the CCK A receptor antagonist devazepide but not by the CCK B receptor antagonist L-365,260

Abstract

The pharmacological mechanisms underlying the hypolocomotion induced by intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injections of cholecystokinin octapeptide sulphated (CCK) in the mouse were examined using selective CCK A and CCK B receptor antagonists. Locomotor activity was measured in photocell cages. CCK (10 μg/kg i.p.) significantly reduced activity in mice tested in the afternoon but not in the morning, indicating a circadian variation in the effect of the peptide. The hypolocomotion induced by i.p. injection of 10 μg/kg CCK and i.c.v. injection of 3.5 μg CCK was reversed by the selective CCK A antagonist devazepide, but not by the selective CCK B antagonist L-365,260. This suggests that CCK-induced hypolocomotion is mediated by CCK A receptors. Larger doses of CCK were required to induce hypolocomotion when injected i.c.v. (3.5 μg per mouse) that when given i.p. (10 μg/kg i.e. 0.2 μg per mouse). Furthermore the latency to onset of the hypolocomotion after i.c.v. injection of CCK was longer than after i.p. injection of CCK. These data suggest that the sedative action of i.c.v. CCK may be due to leakage of the peptide from the brain and subsequent activation of peripheral CCK A receptors. However a role for CCK A receptors in the CNS in mediating hypolocomotion induced by i.c.v. injection of CCK cannot be ruled out on the basis of the present data.