Involvement of free radicals in MDMA-induced neurotoxicity in mice.
3,4-methylenedioxymethamphetamine (MDMA) or ecstasy) is a substituted amphetamine with stimulating and hallucinogenic properties. Administration of MDMA leads to the formation of metabolites responsible for its toxic effects on serotonergic neurons in rats and non-human primates and on dopaminergic neurons in mice. Our findings indicate that overexpression of the human superoxide dismutase gene (Cu/Zn-SOD) abolishes certain effects of MDMA such as the decreased level of dopamine, DOPAC and 5-HT in the striatum, inactivation of certain antioxidant enzymes (CU/ZN-SPD, catalase or glutathione peroxidase) or peroxidation of lipids. These data are in agreement with the implication of free radicals and consequenty of oxidative stress in the mode of action of MDMA.
Cadet
J L
JL
Molecular Neuropsychiatry Section, Division of Intramural Research, Baltimore, MD 21224, USA.
Thiriet
N
N
Jayanthi
S
S
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005609:Free Radicals / Q000009:adverse effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006213:Hallucinogens / Q000009:adverse effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects* / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
D005609:Free Radicals; D006213:Hallucinogens; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D018817:N-Methyl-3,4-methylenedioxyamphetamine