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Role of Nitric Oxide in Methamphetamine Neurotoxicity: Protection by 7‐Nitroindazole, an Inhibitor of Neuronal Nitric Oxide Synthase
Author(s) -
Di Monte Donato A.,
Royland Joyce E.,
Jakowec Michael W.,
Langston J. William
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67062443.x
Subject(s) - meth , methamphetamine , neurotoxicity , nitric oxide , dopamine , dopaminergic , chemistry , tyrosine hydroxylase , pharmacology , nitric oxide synthase , neuroprotection , endocrinology , toxicity , medicine , monomer , organic chemistry , acrylate , polymer
The role of nitric oxide (NO • ) in the neurotoxic effects of methamphetamine (METH) was evaluated using 7‐nitroindazole (7‐NI), a potent inhibitor of neuronal nitric oxide synthase. Treatment of mice with 7‐NI (50 mg/kg) almost completely counteracted the loss of dopamine, 3,4‐dihydroxyphenylacetic acid, and tyrosine hydroxylase immunoreactivity observed 5 days after four injections of 10 or 7.5 mg/kg METH. With the higher dose of METH, this protection at 5 days occurred despite the fact that combined administration of METH and 7‐NI significantly increased lethality and exacerbated METH‐induced dopamine release (as indicated by a greater dopamine depletion at 90 min and 1 day). Combined treatment with 4 × 10 mg/kg METH and 7‐NI also slightly increased the body temperature of mice as compared with METH alone. Thus, the neuroprotective effects of 7‐NI are independent from lethality, are not likely to be related to a reduction of METH‐induced dopamine release, and are not due to a decrease in body temperature. These results indicate that NO • formation is an important step leading to METH neurotoxicity, and suggest that the cytotoxic properties of NO • may be directly involved in dopaminergic terminal damage.