TY - JOUR T1 - Effect of Glucoprivation on Serotonin Neurotoxicity Induced by Substituted Amphetamines JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 831 LP - 839 DO - 10.1124/jpet.102.041277 VL - 303 IS - 2 AU - Jie Yuan AU - Branden J. Cord AU - Una D. McCann AU - Brian T. Callahan AU - George A. Ricaurte Y1 - 2002/11/01 UR - http://jpet.aspetjournals.org/content/303/2/831.abstract N2 - The present studies were conducted to further explore the potential role of metabolic compromise in substituted amphetamine-induced serotonin (5-HT) neurotoxicity. To this end, we examined the glucoprivic effects of 2-deoxy-d-glucose (2-DG) on the 5-HT neurotoxic effects of fenfluramine (FEN) and methylenedioxymethamphetamine (MDMA). Rats were treated with either FEN or MDMA, alone and in combination, with doses of 2-DG known to produce glucoprivic effects at either 22 ± 1 or 28 ± 1°C. At 22 ± 1°C, FEN produced hypothermia, MDMA induced hyperthermia, and both drugs produced significant long-term reductions in regional brain 5-HT neuronal markers. 2-DG did not enhance 5-HT neurotoxicity induced by either FEN or MDMA; indeed, in some instances, it afforded partial neuroprotection. Although 2-DG afforded partial protection from both FEN and MDMA-induced 5-HT neurotoxic changes, it also caused significant hypothermia, raising the possibility that protection was due to a lowered temperature. Increasing the ambient temperature to 28 ± 1°C largely eliminated drug-induced hypothermia and eliminated the neuroprotective effects of 2-DG. Thus, even without the confounding effect of temperature, 2-DG still did not potentiate FEN or MDMA-induced 5-HT neurotoxicity. These findings suggest that the role of metabolic compromise in amphetamine-induced 5-HT neurotoxicity merits further study. The American Society for Pharmacology and Experimental Therapeutics ER -