Behavioral effects of AR-R 15849, a highly selective CCK-A agonist

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 activi ty and specificity, acute administration of AR-R 15849 was found to alter t he 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 r unning wheel, as did fenfluramine. In tests for subchronic anorectic activi ty, daily intraperitoneal injections of AR-R 15849 significantly reduced fo od intake in fasted rats over a 9-day test period with greater efficacy com pared to its nonselective predecessor AR-R 14294 (formerly FPL 14294). The sustained decrease in food intake with AR-R 15849 treatment resulted in a s ignificant reduction in body weight gain over 9 days. Finally, an experimen t designed to determine the effect of caloric deprivation and subchronic dr ug exposure on the overall efficacy of AR-R 15849 indicated that pharmacolo gical tolerance does not develop following subchronic treatment. (C) 1999 E lsevier Science Inc.