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 rel eased cholecystokinin (CCK) acts as a satiety factor. However, interpr etation of these results has been confounded by the fact that devazepi de can enter the brain from the systemic circulation and may increase food intake by a central action. The present study was therefore under taken to confirm the hypothesis that endogenous peripheral CCK is a sa tiety factor by investigating the effects of a novel CCKA receptor ant agonist, 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 significan t 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 ex ogenous peripheral CCK (5 mu g kg(-1), i.p.) on food intake. 4 In agre ement with previous results, devazepide (50-200 mu g kg(-1), i.p.) sig nificantly increased the intake of a test meal in rats. 5 The observat ions that 2-NAP, which is unlikely to penetrate;he blood brain barrier , had no effect on food intake, but that 2-NAP abolished the suppressa nt effect of exogenous peripheral CCK, suggest that endogenously relea sed peripheral CCK is not important as a satiety factor in rats.