Evidence for an involvement of the brain cholecystokinin B receptor in anxiety.
The effect of neuropeptide cholecystokinin (CCK) receptor agonists and antagonists was examined in the rat elevated X-maze model of anxiety. The selective CCK-B receptor antagonists CI-988 (PD 134308) and L-365,260 produced anxiolytic-like effects, whereas MK-329, a CCK-A receptor antagonist, was respectively less potent by factors of 313 and 200. The intracerebroventricular administration of the nonselective CCK receptor agonist caerulein or the selective CCK-B receptor agonist pentagastrin increased dose dependently the level of anxiety. CI-988 dose dependently antagonized the anxiogenic response to pentagastrin but not that induced by pentylenetetrazol. These results strongly suggest that activation of the brain CCK-B receptor induces anxiety and that selective antagonists of this receptor represent a separate class of anxiolytic agents.
Singh
L
L
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge, United Kingdom.
Lewis
A S
AS
Field
M J
MJ
Hughes
J
J
Woodruff
G N
GN
D000818:Animals; D001007:Anxiety; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D002108:Ceruletide / Q000494:pharmacology; D002707:Chlordiazepoxide / Q000008:administration & dosage / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology*
D001570:Benzodiazepinones; D007211:Indoles; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C065599:PD 134308; C058121:L 365260; D008536:Meglumine; D002707:Chlordiazepoxide; D002108:Ceruletide; D002766:Cholecystokinin; D010418:Pentagastrin; D020109:Devazepide