L364,718 antagonizes the cholecystokinin-induced suppression of locomotor activity.
To determine the role of CCK-A receptors in the cholecystokinin (CCK)-induced suppression of locomotor activity in the rat, the ability of the selective CCK-A receptor antagonist L364,718 to block these responses was investigated. Cholecystokinin octapeptide (CCK8) (10, 100 micrograms/kg IP) and caerulein (1, 5, 10 micrograms/kg IP) produced marked reductions in locomotor activity whereas cholecystokinin tetrapeptide (CCK4) (100 micrograms/kg IP) was without effect. The reductions in activity produced by CCK8 (10 micrograms/kg) and caerulein (10 micrograms/kg) were antagonized by L364,718 (100 micrograms/kg IP). In an open field test CCK8 (10 micrograms/kg IP) reduced locomotor activity and total number of rears and increased pause duration. These effects of CCK8 on open-field behaviour were also antagonized by L364,718 (100 micrograms/kg IP). It is concluded that L364,718 is a potent antagonist of the actions of CCK8 and caerulein on locomotor activity, suggesting that the effects of these peptides are mediated by a CCK-A receptor.
Soar
J
J
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge, UK.
Hewson
G
G
Leighton
G E
GE
Hill
R G
RG
Hughes
J
J
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000494:pharmacology*; D002108:Ceruletide / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D012844:Sincalide / Q000494:pharmacology*; D013997:Time Factors
D001570:Benzodiazepinones; D002108:Ceruletide; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide