INHIBITION OF GASTRIC-EMPTYING AND INTESTINAL TRANSIT BY AMPHETAMINE THROUGH A MECHANISM INVOLVING AN INCREASED SECRETION OF CCK IN MALE RATS

1 The effect of amphetamine on gastrointestinal (GI) transit and the p lasma levels of cholecystokinin (CCK) were studied in male rats. 2 Gas tric emptying was inhibited both acutely and chronically by the admini stration of amphetamine. GI transit was decreased by the acute adminis tration of amphetamine but not affected by the chronic administration of amphetamine. 3 Plasma CCK levels were increased dose-dependently by amphetamine. 4 Proglumide, a CCK receptor antagonist, prevented amphe tamine-induced inhibition of gastric emptying and the decrease in GI t ransit in male rats. 5 The selective CCKA receptor antagonist, lorglum ide: dose-dependently attenuated the amphetamine-induced inhibition of gastric emptying in male rats. In contrast, the selective CCKB recept or antagonist, PD 135,158, did not reverse the effect of amphetamine o n gastric emptying. 6 Both lorglumide and PD 135,158 reversed the inhi bitory effect of amphetamine on GI transit in male rats. 7 These resul ts suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK.