THE CCK-A RECEPTOR ANTAGONIST, DEVAZEPIDE, BLOCKS THE ANORECTIC ACTION OF CCK BUT NOT PERIOPHERAL SEROTONIN IN RATS

A role has been proposed for cholecystokinin (CCK)-A-type receptors in mediating the anorectic action produced by serotonergic stimulation in rats. We examined the effect of pretreatment with the CCK-A antagonist devazepide (DVZ) on anorexia produced by peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] or CCK-8 in 3-h food-deprived rats consuming a 30-min test meal of sweetened mash. The anorectic effect of CCK-8 (4.0 nmol/kg, IP) was antagonized in a dose-dependent manner by DVZ (0.03, 0.10, and 0.30 mumol/kg, IP), with even the lowest dose producing a significant reversal. Under identical testing conditions, a supramaximal dose of DVZ (.75 mumol/kg) did not attenuate the reductions in food intake produced by either a moderate (4.0 mumol/kg) or a high dose (10.0 mumol/kg) of 5-HT. These data confirm established findings that the anorectic action of peripheral CCK depends upon CCK-A receptors. However, peripherally administered 5-HT reduces food intake independently of CCKergic function.