Methamphetamine-induced neuronal damage: a possible role for free radicals.
The hypothesis that methamphetamine-induced neuronal damage is mediated by the production of free radicals was evaluated by pretreating rats with either antioxidants or a superoxide dismutase (SOD) inhibitor. It was found that methamphetamine (dose range 6.25-25.0 mg/kg) caused long-lasting depletions of dopamine and serotonin in the striatum and that pretreatment with the antioxidants, ascorbic acid (10-100 mg/kg), ethanol (1 g/kg), mannitol (2 g/kg), or vitamin E (2 g/kg), attenuated these depletions, whereas pretreatment with the superoxide dismutase inhibitor diethyldithiocarbamate (200-400 mg/kg) exacerbated the depletions. The alteration of this effect by four different antioxidants, as well as an inhibitor of superoxidase dismutase, indicated that oxygen-free radicals may have a role in the methamphetamine-induced neurotoxicity.
De Vito
M J
MJ
Department of Toxicology, Rutgers, State University, New Brunswick, New Jersey 08903.
Wagner
G C
GC
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004050:Ditiocarb / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D005609:Free Radicals; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008694:Methamphetamine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors; D014810:Vitamin E / Q000494:pharmacology
D005609:Free Radicals; D014810:Vitamin E; D012701:Serotonin; D000431:Ethanol; D008353:Mannitol; D008694:Methamphetamine; D004050:Ditiocarb; D013482:Superoxide Dismutase; D004298:Dopamine