RAPID AND REVERSIBLE EFFECTS OF METHAMPHETAMINE ON DOPAMINE TRANSPORTERS

Reactive oxygen species decrease dopamine transporter (DAT) function i n vitro. Because of this, and the finding that METH administration cau ses oxygen radical formation in vivo, the effects of METH administrati on on DAT activity in rat striatum were investigated. A single METH in jection caused a dose-dependent (0-15 mg/kg) decrease in [H-3]dopamine uptake into striatal synaptosomes prepared I h after METH administrat ion; an effect attributable to a decreased V-max of [H-3]dopamine upta ke. Similarly, multiple high-dose administrations of METH (10 mg/kg/do se; four doses at 2-h intervals) decreased DAT function. The decreases in DAT activity after either single or multiple METH administrations were reversed 24 h after treatment, [H-3]5HT transport into striatal s ynaptosomes was also affected by METH treatment. Taken together, these data suggest that METH decreases DAT activity, perhaps through a reac tive oxygen species-mediated mechanism. These findings may have import ant implications regarding the role of oxidative events in the physiol ogical regulation of monoaminergic systems.