The relationship between hyperthermia and glycogenolysis in 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats

Although the exact mechanisms involved in the serotonergic neurotoxicity produced by substituted amphetamines are not completely known, evidence suggests that oxidative and/or bioenergetic stress may contribute in the mechanism of neurotoxicity of 3,4-methylenedioxymethamphetamine (NDMA). It has been postulated that MDMA-induced hyperthermia also contributes to the MDMA-induced neurotoxicity. N4DN4A produces brain glycogenolysis, and MDMA-induced hyperthermia appears to mediate this effect. The relationship of MDMA-induced hyperthermia and glycogenolysis in the serotonergic neurotoxicity of MDMA was investigated in the present study. The administration of MDMA (20 mg/kg sc) at an ambient temperature of 24 degreesC produced hyperthermia and brain glycogenolysis in Postnatal Day (PND)21 and PND70 rats; however, long-term reductions in serotonin (5-HT) concentrations in the striatum were detected only in the PND70 rats. Treatment of PND21 and PND70 rats with MDMA at 17 degreesC resulted in neither hyperthermia nor glycogenolysis; nevertheless, long-term reductions in 5-HT concentrations were still evident in the PND70 rats treated with MDNIA. These results support the conclusion that hyperthermia, as well as glycogenolysis, are neither necessary nor sufficient in the serotonergic neurotoxicity of MDNIA. (C) 2004 Elsevier Inc. All rights reserved.