ABDOMINAL VAGOTOMY DISSOCIATES THE ANORECTIC MECHANISMS FOR PERIPHERAL SEROTONIN AND CHOLECYSTOKININ

These studies compared the effects of total abdominal vagotomy (VGX) on ingestive actions produced by peripheral serotonergic and cholecystokinergic (CCKergic) stimulation in rats. Subcutaneous injection of 0.01-0.16 mumol/kg of the serotonin (5-HT) analogue 5-carboxamidotryptamine 5-CT) dose-dependently reduced mash intake equally in VGX rats and their laparotomized (LAP) controls but concurrently stimulated drinking only in the controls. The sulfated octapeptide of cholecystokinin (CCK-8, 4.0 nmol/kg ip) also reduced food intake only in the controls. In a second set of rats, vagotomy did not alter anorexia after intraperitoneal administration of either 2.0 or 8.0 mumol/kg of 5-HT or of 0.03 mumol/kg of 5-CT but abolished. anorexia after a large dose of CCK-8 (8.0 nmol/kg). The completeness of vagotomy was verified histologically by immunohistochemical staining of the vagal bundles for the high molecular weight form of neurofilament-H protein. We report for the first time that 5-CT produces anorexia by a vagally independent mechanism. In contrast, 5-CT stimulates drinking by a pathway that does involve vagal function. Finally, we confirm the prediction that vagotomy dissociates the neural mechanisms for the anorectic action of peripheral 5-HTergic and CCKergic stimulation.