SATIETY INDUCED BY ENDOGENOUS AND EXOGENOUS CHOLECYSTOKININ IS MEDIATED BY CCK-A RECEPTORS IN MICE

To investigate the relative participation of peripheral (CCK-A) and central (CCK-B) cholecystokinin (CCK) receptors in satiety induced by endogenous CCK, we examined the effect of the CCK-A antagonist MK-329 (10-315-mu-g/kg) and the CCK-B antagonist L 365260 (0.1-315-mu-g/kg) on intake of a 20% sucrose solution in mildly food-deprived mice. Intraperitoneal injection of MK-329 elicited a dose-related increase in sucrose consumption with a minimal effective dose of 31.5-mu-g/kg. This dose increased sucrose intake 23% and the highest dose tested, 315-mu-g/kg, increased sucrose intake 63% above baseline. In contrast to MK-329, intraperitoneal administration of L 365260 had no effect on sucrose intake at doses up to 315-mu-g/kg. To examine the contribution of these two CCK receptor subtypes in satiety induced by exogenous CCK, CCK-8 (8-mu-g/kg) was administered alone and in combination with MK-329 and L 365260. MK-329 (10-mu-g/kg) significantly attenuated the satiety effect of CCK-8, and L 365260 (100-mu-g/kg) was without effect. These results suggest that the peripheral CCK receptor subtype mediates satiety induced by endogenous and exogenous CCK in the mouse.