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 microgram/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 equi-osmotic 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 microgram/kg CCK-8 develops through synergy between this peptide and a carbohydrate-sensitive signal generated within the small intestine.