Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum

Stacy E. Stephans, Tim S. Whittingham, Albertina J. Douglas, W. David Lust, Bryan Yamamoto

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

High doses of methamphetamine (METH) produce a long-term depletion in striatal tissue dopamine content. The mechanism mediating this toxicity has been associated with increased concentrations of dopamine and glutamate and altered energy metabolism. In vivo microdialysis was used to assess and alter the metabolic environment of the brain during high doses of METH. METH significantly increased extracellular concentrations of lactate in striatum and prefrontal cortex. This increase was significantly greater in striatum and coincided with the greater vulnerability of this brain region to the toxic effects of METH. To examine the effect of supplementing energy metabolism on METH-induced dopamine content depletions, the striatum was perfused directly with decylubiquinone or nicotinamide to enhance the energetic capacity of the tissue during or after a neurotoxic dosing regimen of METH. When decylubiquinone or nicotinamide was perfused into striatum during the administration of METH, there was no significant effect on METH- induced striatal dopamine efflux, glutamate efflux, or the long-term dopamine depletions measured 7 days later. However, a delayed perfusion with decylubiquinone or nicotinamide for 6 h beginning immediately after the last METH injection attenuated the METH-induced striatal dopamine depletions measured 1 week later. These results support the hypothesis that the compromised metabolic state produced by METH administration predisposes dopamine terminals to the neurotoxic effects of glutamate, dopamine, and/or free radicals.

Original languageEnglish (US)
Pages (from-to)613-621
Number of pages9
JournalJournal of Neurochemistry
Volume71
Issue number2
StatePublished - Aug 1998
Externally publishedYes

Fingerprint

Methamphetamine
Energy Metabolism
Dopamine
Substrates
Corpus Striatum
Niacinamide
Glutamic Acid
Brain
Tissue
Poisons
Microdialysis
Prefrontal Cortex
Free Radicals
Toxicity
Lactic Acid
Perfusion

Keywords

  • Dopamine
  • Energy metabolism
  • Glutamate
  • Methamphetamine
  • Neurotoxicity
  • Striatum

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Cellular and Molecular Neuroscience

Cite this

Stephans, S. E., Whittingham, T. S., Douglas, A. J., Lust, W. D., & Yamamoto, B. (1998). Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum. Journal of Neurochemistry, 71(2), 613-621.

Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum. / Stephans, Stacy E.; Whittingham, Tim S.; Douglas, Albertina J.; Lust, W. David; Yamamoto, Bryan.

In: Journal of Neurochemistry, Vol. 71, No. 2, 08.1998, p. 613-621.

Research output: Contribution to journalArticle

Stephans, SE, Whittingham, TS, Douglas, AJ, Lust, WD & Yamamoto, B 1998, 'Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum', Journal of Neurochemistry, vol. 71, no. 2, pp. 613-621.
Stephans, Stacy E. ; Whittingham, Tim S. ; Douglas, Albertina J. ; Lust, W. David ; Yamamoto, Bryan. / Substrates of energy metabolism attenuate methamphetamine-induced neurotoxicity in striatum. In: Journal of Neurochemistry. 1998 ; Vol. 71, No. 2. pp. 613-621.
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