INHIBITORY EFFECTS OF CHOLECYSTOKININ DEVELOP THROUGH INTERACTION WITH DUODENAL SIGNALS

I previously reported that cholecystokinin octapeptide (CCK-8) had little effect on feeding motivation as indexed by runway performance, but that substantial impairment resulted from the interaction of CCK-8 and prefeeding of sucrose. If the sucrose was sham-fed, potentiation of the effect of CCK-8 was seen only after large doses. The current experiments examined whether synergy between 1 μg/kg CCK-8 and prefeeding could be reproduced using gastric, duodenal, or hepatic-portal infusions. Gastric and duodenal infusions of 30% sucrose were effective; in conjunction with CCK-8 they decreased running speed as substantially as prefeeding did. The duodenal effect was specific. Glucose appeared to be as effective as sucrose, whereas equiosmotic saline and mannitol were not. Intraportal glucose was relatively ineffective; interaction with CCK-8 was seen only after very large infusions, and the resulting running speeds did not approach those seen after prefeeding or gastrointestinal infusions. These results suggest that decreased feeding motivation after 1 μg/kg CCK-8 develops through synergy between this peptide and a carbohydrate-sensitive signal generated within the small intestine. © 1990.