Involvement of free radicals in MDMA-induced neurotoxicity in mice

3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a substituted amphet amine with stimulating and hallucinogenic properties, Administration of MDM A leads to the formation of metabolites responsible for its toxic effects o n serotonergic neurons in rats and non-human primates and on dopaminergic n eurons in mice. Our findings indicate that overexpression of the human supe roxide dismutase gene (Cu/Zn-SOD) abolishes certain effects of MDMA such as the decreased level of dopamine, DOPAC and 5-HT in the striatum, inactivat ion of certain antioxidant enzymes (Cu/Zn-SPD, catalase or glutathione pero xidase) or peroxidation of lipids. These data are in agreement with the imp lication of free radicals and consequently of oxidative stress in the mode of action of MDMA.