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.
Britton
D R
DR
Neuroscience Research Division, Pharmaceutical Discovery, Department 47H Abbott Laboratories, Abbott Park, IL 60064.
Yahiro
L
L
Cullen
M J
MJ
Kerwin
J F
JF
Kopecka
H
H
Nadzan
A M
AM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects*; D012844:Sincalide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000494:pharmacology
D011804:Quinolines; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C063047:A 65186; C063051:butyloxycarbonyl-tryptophyl-methionyl-aspartyl-phenylalaninamide; D012844:Sincalide