Developmental effects of gonadal steriod hormones upon neuroprotection of the nigrostriatal dopaminergic system /

Abstract

The purpose of this report was to determine whether pre-pubertal gonadal steroid hormonal manipulation would alter estrogen's (E) ability to function as a neuroprotectant against methamphetamine (MA)-induced striatal dopamine (DA) depletion in the adult. Male and female CD-l mice were gonadectomized (GNX) at 25 days of age and treated or not with testosterone (T). At 55 days of age mice were treated or not with E and at 62 days of age each of these 8 groups received either MA or vehicle. Striatal dopamine (DA) concentrations and release were measured to provide both a static and dynamic measure of neurotoxicity resulting from MA. As based upon striatal DA concentrations (pg of DA/mg of tissue) GNX at 25 days of age abolishes the capacity for E to function as a neuroprotectant since no differences are apparent between females treated or not with E as adults (4644±612 vs 3683±698) and pre-pubertal GNX failed to enable E to function as a nigrostriatal dopaminergic (NSDA) neuroprotectant in male mice (GNX+T+E = 2973±228: GNX+O+E = 1968±567). These data suggest a crucial role for E at the pre-pubertal period to enable E treatment to function as a neuroprotectant in the adult female. Also, the developmental effects exerted by T during the pre-pubertal period are not responsible for the inability of E to function as a NSDA neuroprotectant in the adult male. However, neuroprotection by E may be present in these same MA-treated males (P=0.612) and females (P=0.43) when compared with their respective vehicle treated controls as defined by potassium stimulated DA release. The divergent results in these data indicate the importance of the parameter used to measure neuroprotection. T and E have differential modulatory effects on DA function that are not different between P25 gonadectomized female and male mice.