Protective effect of tamoxifen, a synthetic non-steroidal antiestrogen, on phenelzine and 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical generation in rat striatum.

The present study examined whether tamoxifen 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 (0.1 mM 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 pressent study is the first demonstration showing the protective effect of tamoxifen on *OH generation induced by phenelzine enhanced MPP+ by suppressing DA efflux.