RAT STRIATAL LEVELS OF THE ANTIOXIDANT GLUTATHIONE ARE DECREASED FOLLOWING BINGE ADMINISTRATION OF METHAMPHETAMINE

Involvement of the glutathione antioxidant system is a characteristic feature of oxidative stress. We examined the influence of binge (4 x 2 0 mg/kg every 5 h) and chronic daily (20 mg/kg per day for 10 days) ad ministration of methamphetamine (MA) on brain levels of total glutathi one and major glutathione-related enzymes (glutathione peroxidase and reductase; gamma-glutamyltranspeptidase; glucose-6-phosphate dehydroge nase) in the rat. Binge, but not chronic MA administration was associa ted with a regionally specific reduction (-17%, P < 0.05) in striatal levels of glutathione 3 h after the last dose of MA, whereas striatal levels of the glutathione-related enzymes were normal. Although the ma gnitude of the reduction was only modest, these data are compatible wi th a more severe glutathione decrease localized to dopamine/serotonin nerve terminal areas. Our observations provide further evidence in sup port of the oxidative stress hypothesis of MA neurotoxicity and indire ctly suggest that drugs designed to increase glutathione might protect against such damage. (C) 1998 Elsevier Science Ireland Ltd. All right s reserved.