Intracerebroventricular cholecystokinin A-receptor antagonist does not reduce satiation by endogenous CCK.
Suppression of sham feeding by exogenous CCK-8 or intraintestinal oleate infusion is attenuated by peripheral administration of the CCK-A receptor antagonist, devazepide, but not by the CCK-B antagonist, L365260. Likewise, systemically administered devazepide increases food intake by real feeding rats. These results suggest that endogenous CCK participates in the reduction of food intake by intestinal oleate and ingested food. Although originally categorized as a "peripheral" receptor subtype, the CCK-A receptor is also present in the brain. In an effort to examine whether devazepide acts in the brain or in the periphery to attenuate suppression of food intake by intraintestinal oleate, we injected devazepide into the lateral or fourth cerebral ventricles of intraintestinally infused, sham-fed rats. We also compared the ability of intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) devazepide to elicit increased food intake in real feeding rats. Doses of devazepide that were sufficient to attenuate or abolish oleate-induced suppression of sham feeding, when administered i.p., failed to attenuate suppression of intake when administered i.c.v., i.p. devazepide also was more effective than i.c.v. devazepide for attenuation of the suppression of sham feeding by i.p. injection of exogenous CCK-8. Finally, i.c.v. devazepide was ineffective for increasing real food intake, whereas the same dose administered i.p. significantly increased food intake. Our results do not support participation of brain CCK-A receptors in the suppression of food intake by exogenous CCK, or by endogenous CCK released after intraintestinal oleate infusion, or food intake.
Brenner
L A
LA
Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman 99164-6520, USA.
Ritter
R C
RC
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D002766:Cholecystokinin / Q000502:physiology*; D020109:Devazepide; D004435:Eating / Q000187:drug effects; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007441:Intubation, Gastrointestinal; D008297:Male; D019301:Oleic Acid / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D011949:Receptors, Cholecystokinin; D019301:Oleic Acid; D002766:Cholecystokinin; D020109:Devazepide