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 very limited information on the role of testosterone (T) in this capacity. In the present report, the effects of T on methamphetamine (MA) induced neurotoxicity of the NSDA system were examined in gonadectomized female and male CD-1 mice. In Experiment 1, striatal dopamine (DA) concentrations and output from T-treated ovariectomized mice were not significantly different from 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 ovariectomized 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-treated orchidectomized mice following MA. The results of Experiment 2 indicate 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 gender differences which are observed in animal models of NSDA neurotoxicity and in Parkinson's disease.
Gao
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Department of Anatomy, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, PO Box 95, Rootstown, OH 44272, USA.
Dluzen
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D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004343:Drug Implants; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D009919:Orchiectomy; D010052:Ovariectomy; D011188:Potassium / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*
D004343:Drug Implants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D013739:Testosterone; D008694:Methamphetamine; D011188:Potassium; D004298:Dopamine