title: Effect of the selective CCKB receptor antagonist LY288513 on conditioned fear stress in rats.
abstract: In order to investigate the involvement of cholecystokinin (CCK) in the regulation of anxiety, the effect of the selective non-peptide CCKB receptor antagonist LY288513 ((4S, 5R)-N-(4-bromophenyl)-3-oxo-4,5-diphenyl-1-1-pyrazolidinecarboxamide+ ++) on freezing behavior induced by conditioned fear stress was examined using a time-sampling procedure. Rats were individually subjected to 5 min of inescapable electric footshock in a shock chamber. Twenty-four hours after the footshock, the rats were again placed in the shock chamber and observed for 5 min without shocks: this procedure is termed conditioned fear stress. Subcutaneous administration of LY288513 30 min before footshock (0.3 mg/kg) and 30 min before conditioned fear stress (0.03 mg/kg) reduced conditioned freezing. This indicates that LY288513 blocked both the acquisition and expression of conditioned fear. The relatively selective non-peptide CCKA receptor antagonist, lorglumide (D, L-4-(3,4-dichlorobenzoylamino)-5-(diphentylamino)-5-oxo-pent anoic acid), blocked the expression of conditioned fear, though only at a high dose (1.0 mg/kg). The peripheral non-peptide CCKA/B receptor antagonist, loxiglumide (D, L-4-(3,4-dichlorobenzoylamino)-5- (N-3-methoxypropyl-pentylamino)-5-oxo-pentanoic acid), failed to do so. These results suggest that brain CCKB receptors are involved in the regulation of anxiety.
authors: Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan.
authors: T
authors: T
authors: Izumi
authors: T
authors: T
authors: Inoue
authors: K
authors: K
authors: Tsuchiya
authors: S
authors: S
authors: Hashimoto
authors: T
authors: T
authors: Ohmori
authors: T
authors: T
authors: Koyama
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D005239:Fear; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013312:Stress, Physiological / Q000503:physiopathology
chemical_list: D006727:Hormone Antagonists; D011720:Pyrazoles; D011949:Receptors, Cholecystokinin; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; C053737:loxiglumide; D011377:Proglumide; C048181:lorglumide