Effects of 2-deoxy-D-glucose on methamphetamine-induced dopamine and serotonin neurotoxicity

Brian Callahan, Jie Yuan, Gretchen Stover, George Hatzidimitriou, George Ricaurte

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanisms underlying the neurotoxic actions of methamphetamine (METH) and related substituted amphetamines are unknown. Previous studies with 2-deoxyglucose (2-DG) have suggested mat METH-induced neurotoxicity may involve exhaustion of intracellular energy stores. However, because 2-DG also produces hypothermic effects, and because METH's neurotoxic actions are highly susceptible to thermoregulatory influence, previous findings with 2- DG are difficult to interpret. The present studies were undertaken to further examine the influence of 2-DG's glucoprivic and thermic effects in me context of METH-induced dopamine (DA) and serotonin (5-HT) neurotoxicity. 2-DG protected against METH-induced DA neurotoxicity in both rats and mice. In both species, 2-DG, alone or in combination with METH, produced hypothermic effects. METH's toxic effects on brain 5-HT neurons were either unaffected or exacerbated by 2-DG, depending on species, brain region, and dose of METH tested. These results indicate that different mechanisms may underlie METH- induced DA and 5-HT neurotoxicity, and suggest that, as compared with 5-HT neurons, DA neurons are more susceptible to temperature influence, whereas 5- HT neurons are more vulnerable than DA neurons to metabolic compromise. Additional studies are needed to further assess the role of energy stores in the neurotoxic effects of METH and related drugs.

Original languageEnglish (US)
Pages (from-to)190-197
Number of pages8
JournalJournal of Neurochemistry
Volume70
Issue number1
DOIs
StatePublished - Jan 1998

Keywords

  • 2- Deoxyglucose
  • Dopamine
  • Glu cose metabolism
  • Methamphetamine
  • Neurotoxicity
  • Serotonin
  • Temperature

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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