Gender differences in modulatory effects of tamoxifen upon the nigrostriatal dopaminergic system.

Gender differences in modulatory effects of tamoxifen upon the nigrostriatal dopaminergic system.

Dluzen Dean E; Mickley Katherine R

Pharmacology, biochemistry, and behavior

2005

2005-01

It has been demonstrated that the gonadal steroid hormone estrogen can exert neuroprotective effects upon the nigrostriatal dopaminergic (NSDA) system against methamphetamine (MA)-induced neurotoxicity in female, but not male, mice. In contrast, the anti-estrogen, tamoxifen (TMX) can function as a NSDA neuroprotectant within both female and male mice. In an attempt to understand these effects of TMX, the effects of this anti-estrogen upon both behavioral and neurochemical indices of NSDA function were examined within female and male mice following treatment with MA. In general, TMX exerted markedly different (bi-directional) effects upon NSDA function between female and male mice. Notably, treatment with TMX resulted in a relative decrease in striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations within male mice and a relative increase in female mice when treated with MA to produce a significant gender difference. Similar effects were obtained for locomotor behaviors related with NSDA function. That is, TMX produced increases in horizontal activity, number of movements and total distance traveled within

*Sex Characteristics; Animals; Corpus Striatum/*drug effects/metabolism; Dopamine/*metabolism; Female; Male; Mice; Motor Activity/drug effects/physiology; Substantia Nigra/*drug effects/metabolism; Tamoxifen/*pharmacology

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