Hypolocomotion induced by peripheral or central injection of CCK in the mouse is blocked by the CCKA receptor antagonist devazepide but not by the CCKB receptor antagonist L-365,260.
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 CCKA and CCKB receptor antagonists. Locomotor activity was measured in photocell cages. CCK (10 micrograms/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 micrograms/kg CCK and i.c.v. injection of 3.5 micrograms CCK was reversed by the selective CCKA antagonist devazepide, but not by the selective CCKB antagonist L-365,260. This suggests that CCK-induced hypolocomotion is mediated by CCKA receptors. Larger doses of CCK were required to induce hypolomotion when injected i.c.v. (3.5 micrograms per mouse) than when given i.p. (10 micrograms/kg i.e. 0.2 microgram 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 CCKA receptors. However a role for CCKA 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.
O'Neill
M F
MF
Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Harlow, Essex, U.K.
Dourish
C T
CT
Iversen
S D
SD
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002940:Circadian Rhythm; D020109:Devazepide; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012844:Sincalide / Q000008:administration & dosage / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide