Effect of glucoprivation on serotonin neurotoxicity induced by substituted amphetamines

Jie Yuan, Branden J. Cord, Una D. McCann, Brian T. Callahan, George A. Ricaurte

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)831-839
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume303
Issue number2
DOIs
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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