2-Naphthalenesulphanyl-L-aspartyl-2-(phenethyl) amide (2-NAP) and food intake in rats: evidence that endogenous peripheral CCK does not play a major role as a satiety factor.

1. The demonstration that systemic administration of the CCKA receptor antagonist, devazepide, increases food intake in rats has provided the strongest support for the hypothesis that endogenous peripherally released cholecystokinin (CCK) acts as a satiety factor. However, interpretation of these results has been confounded by the fact that devazepide can enter the brain from the systemic circulation and may increase food intake by a central action. The present study was therefore undertaken to confirm the hypothesis that endogenous peripheral CCK is a satiety factor by investigating the effects of a novel CCKA receptor antagonist, 2-NAP, which is unlikely to cross the blood brain barrier, on food intake in rats. 2. 2-NAP (1-16 mg kg-1, i.p.) had no significant effects on the intake of a test meal in rats. 3. Pretreatment of rats with 2-NAP (2 mg kg-1, s.c.) abolished the inhibitory effects of exogenous peripheral CCK (5 micrograms kg-1, i.p.) on food intake. 4. In agreement with previous results, devazepide (50-200 micrograms kg-1, i.p.) significantly increased the intake of a test meal in rats. 5. The observations that 2-NAP, which is unlikely to penetrate the blood brain barrier, had no effect on food intake, but that 2-NAP abolished the suppressant effect of exogenous peripheral CCK, suggest that endogenously released peripheral CCK is not important as a satiety factor in rats.