Cholecystokinin-induced satiety depends on activation of 5-HT1C receptors

B. Poeschla, J. Gibbs, K. J. Simansky, D. Greenberg and G. P. Smith Department of Psychiatry, Cornell University Medical College, White Plains, New York. To investigate the dependence of the satiating action of cholecystokinin on serotonergic function in rats, we examined the effects of systemic pretreatment with serotonin (5-HT) antagonists of varying selectivity for 5-HT receptor subtypes on suppression of food intake induced by systemic administration of cholecystokinin octapeptide (CCK-8). Mianserin, a 5-HT1C/2-selective antagonist, significantly attenuated the satiating action of CCK-8. Ketanserin, a 5-HT2 antagonist, and three 5-HT3 antagonists, MDL-72222, ICS 205-930, and ondansetron, however, had no effect on the satiating action of CCK-8. These results demonstrate that the satiating action of exogenous CCK depends on activation of 5-HT1 (probably 5-HT1C) receptors and that activation of 5-HT2 or 5-HT3 receptors is not required.