Intravenous infusion of CCKA-receptor antagonist increases food intake in rats

To test the hypothesis that endogenous cholecystokinin (CCK) released from the small intestine by ingested food produces a satiating effect by acting at CCKA-receptors, we measured the effect of slow continuous intravenous infusions of three doses of MK-329, a potent and selective CCKA-antagonist, on food intake during 2.5-h tests in 13 Sprague-Dawley male rats after 1 h of food deprivation. MK-329 increased food intake significantly and the lowest dose tested (0.5 mg.kg-1.h-1) produced the most consistent effect on cumulative intake. Part of the increased food intake under these conditions was due to a decrease in the satiating effect of food ingested at the first meal on the postprandial intermeal interval. These results are consistent with, but do not prove, the hypothesis that the satiating effect of endogenous CCK released from the small intestine by ingested food is mediated by CCKA-receptors.