Journal
JOURNAL OF NEUROCHEMISTRY
Volume 76, Issue 3, Pages 745-749Publisher
BLACKWELL SCIENCE LTD
DOI: 10.1046/j.1471-4159.2001.00029.x
Keywords
copper zinc superoxide dismutase; dopamine; methamphetamine; neurotoxicity; nitric oxide synthase; peroxynitrite
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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 revels of 3-NT increased in the striatum of wild-type mice treated with multiple doses of METH (4 x 10 mg/kg, 2 h interval) as compared with the controls. However, no significant production or 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-TS mice. These data further confirm that METH causes its neurotoxic effects via the production of peroxynitrite.
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