EFFECTS OF TESTOSTERONE UPON MPTP-INDUCED NEUROTOXICITY OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM OF C57 B1 MICE/

We have recently reported that treatment of gonadectomized female and male C57/B1 mice with the gonadal steroid hormone, estrogen, reduced n igrostriatal dopaminergic neurotoxicity resulting from the Parkinson's -like inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPT P). In the present report we examined whether the predominantly male g onadal steroid hormone, testosterone, would similarly modulate MPTP-in duced neurotoxicity. Male C57/B1 mice were assigned to one of the foll owing five treatment conditions: (1) Intact, (2) Orchidectomized, (3) Intact + MPTP, (4) Orchidectomized + Testosterone + MPTP and (5) Orchi dectomized + MPTP. Corpus striatal and olfactory tubercle dopamine, DO PAC and norepinephrine concentrations were determined from the animals within each of the five treatment conditions. Orchidectomy alone fail ed to alter striatal dopamine and DOPAC concentrations, with levels ob tained being similar to that of Intact animals, MPTP treatment signifi cantly reduced striatal dopamine and DOPAC concentrations, regardless of hormonal condition of the animal. Similar results were obtained for olfactory tubercle determinations, with the exception that DOPAC leve ls from Orchidectomized mice were significantly greater than Intact ma les. No significant differences were obtained for norepinephrine withi n either brain area sampled. These results show that unlike estrogen, testosterone is devoid of any capacity to modulate nigrostriatal dopam inergic neurotoxicity resulting from MPTP. These findings may be relat ed to the gender differences which exist in the prevalence of Parkinso n's disease.