Peroxynitrite plays a role in methamphetamine-induced dopaminergic neurotoxicity: Evidence from mice lacking neuronal nitric oxide synthase gene or overexpressing copper-zinc superoxide dismutase

Syed Z. Imam, Glenn D. Newport, Yossef Itzhak, Jean L. Cadet, Fakhrul Islam, William Slikker, Syed F. Ali

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

The use of methamphetamine (METH) leads to neurotoxic effects in mammals. These neurotoxic effects appear to be related to the production of free radicals. To assess the role of peroxynitrite in METH-induced dopaminergic, we investigated the production of 3-nitrotyrosine (3-NT) in the mouse striatum. The levels of 3-NT increased in the striatum of wild-type mice treated with multiple doses of METH (4 × 10 mg/kg, 2 h interval) as compared with the controls. However, no significant production of 3-NT was observed either in the striata of neuronal nitric oxide synthase knockout mice (nNOS -/-) or copper-zinc superoxide dismutase overexpressed transgenic mice (SOD-Tg) treated with similar doses of METH. The dopaminergic damage induced by METH treatment was also attenuated in nNOS-/- or SOD-Tg mice. These data further confirm that METH causes its neurotoxic effects via the production of peroxynitrite.

Original languageEnglish (US)
Pages (from-to)745-749
Number of pages5
JournalJournal of neurochemistry
Volume76
Issue number3
DOIs
StatePublished - Feb 19 2001

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Keywords

  • Copper zinc superoxide dismutase
  • Dopamine
  • Methamphetamine
  • Neurotoxicity
  • Nitric oxide synthase
  • Peroxynitrite

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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