nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice

Yossef Itzhak, Julio L. Martin, Syed F. Ali

Research output: Contribution to journalArticle

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Abstract

Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity. (C) 2000 Lippincott Williams and Wilkins.

Original languageEnglish (US)
Pages (from-to)2943-2946
Number of pages4
JournalNeuroreport
Volume11
Issue number13
DOIs
StatePublished - Sep 11 2000

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Keywords

  • 3-Bromo-7-nitroindazole
  • 7-Nitroindazole
  • Dopaminergic neurotoxicity
  • Hyperthermia
  • Nitric oxide (NO)
  • S-Methylthiocitruline

ASJC Scopus subject areas

  • Neuroscience(all)

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