Methamphetamine enhances 1-methyl-4-phenylpyridinium ion-induced hydroxyl radical generation in the rat striatum

We determined the methamphetamine (MA), a potent dopamine (DA) releaser, enhances 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical (&z.rad;OH) generation in the rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 nmol/microl/min) was infused through a microdialysis probe to detect the generation of .OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. After administration of MA (5 mg/kg i.v., every 2 h, four times), MA drastically increased DA release and the &z.rad;OH formation. When iron (II) was administered to the MA-treated animals, a marked elevation of DHBA was observed, compared with MPP(+)-only treated animals, that showed a positive linear correlation between DA and .OH formation trapped as DHBA (R(2)=0.985) in the dialysate. These results suggest that MA enhances the &z.rad;OH products of efflux/oxidation due to MPP(+).