INFLUENCE OF GONADAL-HORMONES ON SEXUAL DIFFERENCES IN SENSITIVITY TOMETHAMPHETAMINE-INDUCED NEUROTOXICITY

The administration of high doses of methamphetamine to mice causes lon g-lasting depletions of striatal dopamine to a greater extent in males than in females. Likewise, the incidence of Parkinson's disease is hi gher in males than in females. The present study investigated the role s of estrogen and testosterone in mediating the dopamine depletion ind uced 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 wa s 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 change d the magnitude of the methamphetamine-induced dopamine depletion. Thu s, the reduced sensitivity of female mice to methamphetamine may be in dependent of physiological gonadal hormones.