Effect of dexfenfluramine on metabolic and neurochemical measures in restraint-stressed ob/ob mice

Genetically obese (ob/ob) and lean C57BL/6J mice were subjected to 1 h acute restraint stress, and the effects on plasma glucose and corticosterone, and brain amines, were assessed relative to nonrestrained groups. Some mice were treated with dexfenfluramine (DFEN) prior to restraint. Compared with their lean counterparts, ob/ob mice had elevated basal plasma levels of both glucose and corticosterone. Both lean and ob/ob showed comparable absolute restraint-induced increments in these measures, but the fractional increase was much smaller in ob/ob. Metabolism of NE, DA and 5-HT was also assessed from the ratio of the metabolite-to-amine in various brain regions. Obese mice had smaller restraint-related increases in monoamine metabolism than lean their counterparts. Acute DFEN increased corticosterone, but tended to reduce the restraint-induced elevations in glucose and monoamine metabolism.