The effects of a peripherally acting cholecystokinin, receptor antagonist on food intake in rats: implications for the cholecystokinin-satiety hypothesis

The observation that systemic administration of the peptide cholecystokinin (CCK) inhibits food intake in mammalian species has led to the hypothesis that endogenous peripheral CCK released from the small intestine during a meal acts as a satiety factor. It was predicted that if CCK does play an important role in satiety, then systemic administration of a specific CCK receptor antagonist should block the effects of the endogenous peptide released during a meal and increase food intake. The present study was undertaken to test the hypothesis by investigating the effects of the cholecystokinin(1) (CCK1) receptor antagonist N-alpha-3'-quinolinoyl-D-Glu-N,N-dipentylamide dicyclohexylammonium (A70104), which is unlikely to cross the blood-brain barrier, on food intake in rats. A70104 (20-200 mug/kg, i.p.) had no any significant effect on the intake of a test meal in rats under different experimental conditions. However, pretreatment of rats with A70104 (50 mug/kg, i.p.) abolished the inhibitory effects of exogenous peripheral CCK (5 mug/kg, i.p.) on food intake. The findings that A70104 had no effect on food intake when administered on its own, but abolishes the suppressant effect of exogenous peripheral CCK, suggest that endogenously released peripheral CCK does not play an important role as a satiety factor in rats. (C) 2003 Elsevier Science B.V. All rights reserved.