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

Brain Res. 2001 Feb 16;892(1):63-9. doi: 10.1016/s0006-8993(00)03221-2.


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.

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Drug Implants
  • Female
  • Male
  • Methamphetamine / toxicity*
  • Mice
  • Neuroprotective Agents / pharmacology
  • Neurotoxins / toxicity*
  • Orchiectomy
  • Ovariectomy
  • Potassium / pharmacology
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism*
  • Testosterone / administration & dosage
  • Testosterone / pharmacology*


  • Drug Implants
  • Neuroprotective Agents
  • Neurotoxins
  • Testosterone
  • Methamphetamine
  • Potassium
  • Dopamine