Behavioral Effects of AR-R 15849, a Highly Selective CCK-A Agonist

• Published in: Pharmacology, biochemistry and behavior Vol. 62; no. 3; pp. 549 - 557
• Main Authors: Simmons, R.D, Kaiser, F.C, Hudzik, T.J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-03-1999; Elsevier Science
• Subjects: Animals; Appetite Depressants - pharmacology; AR-R 14294; AR-R 15849; Behavior, Animal - drug effects; Biological and medical sciences; Body Weight - drug effects; CCK-A receptor; Cholecystokinin; Cholecystokinin - analogs & derivatives; Cholecystokinin - pharmacology; Drug Tolerance; Eating - drug effects; Fenfluramine; Fenfluramine - pharmacology; Food intake; General and cellular metabolism. Vitamins; Male; Medical sciences; Motor activity; Motor Activity - drug effects; Operant feeding paradigm; Pharmacology. Drug treatments; Rats; Receptor, Cholecystokinin A; Receptors, Cholecystokinin - agonists; Running wheel; Subchronic treatment; Time Factors; Tolerance; Weight loss; Running wheel; AR-R 15849; Food intake; CCK-A receptor; Motor activity; Weight loss; Tolerance; Fenfluramine; Subchronic treatment; Cholecystokinin; AR-R 14294; Operant feeding paradigm; Agonist; Intraperitoneal administration; Feeding behavior; Rat; Rodentia; CCK A Cholecystokinin receptor; Biological activity; Vertebrata; Mammalia; Animal; Anorectic; Motricity; Comparative study
• DOI: 10.1016/S0091-3057(98)00186-5
• EISSN: 1873-5177
• ISSN: 0091-3057

The behavioral effects of AR-R 15849, a novel cholecystokinin agonist with high affinity and selectivity for the CCK-A receptor subtype, were examined. Initially, using an operant feeding paradigm to test for anorectic activity and specificity, acute administration of AR-R 15849 was found to alter the intake and pattern of feeding in a manner similar to prefeeding. Further, AR-R 15849 did not induce compensatory feeding as did CCK-8, and did not affect performance on running rates of responding, or motor activity on a running wheel, as did fenfluramine. In tests for subchronic anorectic activity, daily intraperitoneal injections of AR-R 15849 significantly reduced food intake in fasted rats over a 9-day test period with greater efficacy compared to its nonselective predecessor AR-R 14294 (formerly FPL 14294). The sustained decrease in food intake with AR-R 15849 treatment resulted in a significant reduction in body weight gain over 9 days. Finally, an experiment designed to determine the effect of caloric deprivation and subchronic drug exposure on the overall efficacy of AR-R 15849 indicated that pharmacological tolerance does not develop following subchronic treatment.