Estrogen, but not testosterone, attenuates methamphetamine-evoked dopamine output from superfused striatal tissue of female and male mice.

Estrogen, but not testosterone, attenuates methamphetamine-evoked dopamine output from superfused striatal tissue of female and male mice.

Myers R E; Anderson L I; Dluzen D E

Neuropharmacology

2003

2003-04

The gonadal steroid hormone, estrogen, has the capacity to function as a neuroprotectant against methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic system within female, but not male, mice. In an attempt to understand some of the bases for this effect of estrogen, the incipient effects of MA upon evoked dopamine output from superfused striatal tissue fragments of gonadectomized female and gonadectomized as well as intact male mice were evaluated under conditions where estrogen (or testosterone) was present in the medium. The amount of dopamine evoked by MA was significantly reduced when estrogen was co-infused with MA. This attenuation was obtained with striatal tissue fragments of gonadectomized female and gonadectomized and intact male mice. In contrast to estrogen, co-infusion of testosterone failed to produce an overall statistically significant change in MA-evoked dopamine output within superfused striatal tissue fragments of gonadectomized female and male mice. In this way, the gonadal steroid hormones, estrogen and testosterone, exert differential modulatory effects upon MA-evoked dopamine output from superfused striatal tissue fragments. However, similar effects to these gonadal steroid hormones were observed between gonadectomized female and gonadectomized or intact male mice. These data reveal an absence of a sexual dimorphism in striatal responsiveness with regard to estrogen's ability to alter MA-evoked DA output. Accordingly, the sexually dimorphic capacity for estrogen to function as a neuroprotectant may involve a composite of actions upon the nigrostriatal dopaminergic system involving events/sites other than the initial stimulation of dopamine output.

Animals; Corpus Striatum/*drug effects/metabolism; Dopamine/*metabolism; Estrogens/*metabolism; Female; In Vitro Techniques; Male; Methamphetamine/*pharmacology; Mice; Orchiectomy; Ovariectomy; Perfusion; Testosterone/*metabolism

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