Influence of gonadal hormones on sexual differences in sensitivity to methamphetamine-induced neurotoxicity

The administration of high doses of methamphetamine to mice causes long-lasting depletions of striatal dopamine to a greater extent in males than in females. Likewise, the incidence of Parkinson's disease is higher in males than in females. The present study investigated the roles of estrogen and testosterone in mediating the dopamine depletion induced by methamphetamine. Male and female mice received four cumulative SC doses of methamphetamine (10 mg/kg) at two hour intervals and were sacrificed two weeks later for HPLC analysis of striatal monoamines. Intact male mice were found to have a 76% dopamine depletion, which was significantly greater than the 37% depletion exhibited by the intact female mice. Neither removal of the ovaries nor removal of the testes one month prior to the methamphetamine treatment significantly changed the magnitude of the methamphetamine-induced dopamine depletion. Thus, the reduced sensitivity of female mice to methamphetamine may be independent of physiological gonadal hormones.