Nitric Oxide Is a Mediator of Methamphetamine (METH)‐Induced Neurotoxicity
- 1 October 1996
- journal article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 801 (1) , 174-186
- https://doi.org/10.1111/j.1749-6632.1996.tb17440.x
Abstract
METH is a monoaminergic toxic that destroys dopamine terminals in vivo. Oxidative mechanisms associated with DA metabolism are thought to play an important role in its toxic effects. These ideas were supported by the demonstration that CuZn-superoxide dismutase (CuZnSOD) transgenic mice were protected against the toxic effects of the drug. In the present study, we sought to determine if nitric oxide (NO) production was also involved in METH-induced neurotoxicity using primary cultures obtained from fetal rat mesencephalon. METH caused dose- and time-dependent cell death in vitro. Blockade of nitric oxide (NO) formation with several nitric oxide (NO) synthase blockers attenuated METH-mediated toxicity. Moreover, inhibition of ADP-ribosylation with nicotinamide and benzamide also provided protection against the toxicity of the drug. These results, together with our previous results in transgenic mice, support a role for free radicals in METH-induced toxic effects.Keywords
This publication has 38 references indexed in Scilit:
- Methamphetamine (METH) causes reactive gliosis in vitro: Attenuation by the ADP-ribosylation (ADPR) inhibitor, benzamideLife Sciences, 1994
- A radical hypothesis for neurodegenerationTrends in Neurosciences, 1993
- Dopamine-glutamate interactions in methamphetaminc-induced neurotoxicityJournal Of Neural Transmission-Parkinsons Disease and Dementia Section, 1993
- Differing Neurotoxic Potencies of Methamphetamine, Mazindol, and Cocaine in Mesencephalic CulturesJournal of Neurochemistry, 1993
- Survival of developing dopaminergic neurons in reaggregate tissue culture following treatment with methamphetamineNeuroscience Letters, 1991
- A unifying theory of movement and madness: Involvement of free radicals in disorders of the isodendritic core of the brainstemMedical Hypotheses, 1988
- Neurotoxic effects of methamphetamine assessed in three-dimensional reaggregate tissue culturesDevelopmental Brain Research, 1987
- Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide.Journal of Clinical Investigation, 1986
- Methamphetamine-Induced Depression of Monoamine Synthesis in the Rat: Development of ToleranceJournal of Neurochemistry, 1985
- Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamineBrain Research, 1980