Protective effect of tamoxifen on 1-methyl-4-phenylpyridine-induced hydroxyl radical generation in the rat striatum.

We examined whether tamoxifen could suppress 1-methyl-4-phenylpyridine (MPP(+))-induced hydroxyl radical generation in the extracellular fluid of rat striatum, using in vivo microdialysis system. MPP(+) (5 mM) enhanced generation of hydroxyl radicals with concomitant increased efflux of dopamine. Tamoxifen (1--100 microM) dose-dependently suppressed the hydroxyl radical formation induced by MPP(+). Tamoxifen (100 microM) significantly attenuated dopamine efflux induced by MPP(+). The result in the present study is the first demonstration showing the protective effect of tamoxifen on hydroxyl radical generation induced by MPP(+) by suppressing dopamine efflux.