EFFECT OF A NOVEL CCK(A) RECEPTOR ANTAGONIST (2-NAP) ON THE REDUCTIONIN FOOD-INTAKE PRODUCED BY CCK IN PIGS

The effect of a novel CCK(A) receptor antagonist aphthalenesulphanyl-L -aspartyl-2-(phenethyl)amide, sodium salt (2-NAP) on the reduction of food intake induced by exogenous CCK, administered centrally or periph erally, has been examined in pigs. 2-NAP is hydrophilic and should not readily cross the blood-brain barrier. Intravenous (IV) 2-NAP (20 or 40 mg/kg) injected prior to IV CCK-8S (1 mug/kg) abolished the inhibit ory effect of CCK-8S on operant food intake in hungry pigs. Intravenou s injections of 2-NAP (20 and 30 mg/kg) prior to the administration of intracerebroventricular (ICV) injection of CCK-8S (1 mug) did not aff ect the inhibitory action of ICV CCK-8S on food intake. ICV injection of 2-NAP (5 mg) abolished the inhibitory effect on food intake of ICV CCK-8S (1 mug). The results indicate that 2-NAP does not cross the blo od-brain barrier readily and that central and peripheral administratio n of CCK-8S inhibits feeding by different mechanisms. Neither ICV nor IV injectionof 2-NAP altered food intake when injected alone.