Tamoxifen protect against hydroxyl radical generation induced by phenelzine in rat striatum

The present study was examined whether tamoxifen, a synthetic nonsteroidal antiestrogen, could suppress antidepressant drug phenelzine can increase an active dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical (OH) generation in the extracellular fluid of rat striatum, using in vivo microdialysis system. Rats were anesthetized, and sodium salicylate (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. Infusion of phenelzine (100 microM or 0.1 nmol/microl/min) into the striatum drastically increased dopamine (DA) efflux and the OH formation, trapped as 2,3-DHBA by the possible increased production of MPP(+). However, tamoxifen (100 microM) significantly suppressed phenelzine enhanced DA efflux and OH formation by MPP(+). These results in the present study is the first demonstration showing the protective effect of tamoxifen on OH generation induced by phenelzine enhanced MPP(+) by suppressing DA efflux.