The effect of testosterone upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system

The gonadal steroid hormone estrogen (E) can function as a neuroprotectant of nigrostriatal dopaminergic (NSDA) neurotoxicity, however, there exists v ery limited information on the role of testosterone (T) in this capacity. I n the present report, the effects of T on methamphetamine (MA) induced neur otoxicity of the NSDA system were examined in gonadectomized female and mal e CD-1 mice. In Experiment I, striatal dopamine (DA) concentrations and out put from T-treated ovariectomized mice were not significantly different fro m that of non-T-treated mice following MA. These results suggest that T is not functioning as a modulator of MA-induced NSDA neurotoxicity in ovariect omized CD-1 mice. In Experiment 2, there were no significant differences in DA concentrations or output among T-treated, non-T-treated as well as E-tr eated orchidectomized mice following MA. The results of Experiment 2 indica te that the neuroprotective effect of E reported within ovariectomized mice is not seen in male mice. Nor does T appear to function as a modulator of MA neurotoxicity in male mice. These effects of T and E upon the MA induced neurotoxicity of the NSDA system have important implications for the gende r differences which are observed in animal models of NSDA neurotoxicity and in Parkinson's disease. (C) 2001 Elsevier Science B.V. All rights reserved .