Sexual differences and estrous cycle in methamphetamine-induced dopamine and serotonin depletions in the striatum of mice

Four consecutive doses (10 mg/kg) of methamphetamine, s.c., produced a substantial striatal dopamine depletion in both sexes of BALB/c and C57BL/6J mice. Male C57BL/6J mice exhibited greater dopamine depletions in the striatum compared to female C57BL/6J mice. In contrast, male and female BALB/c mice demonstrated an equivalent magnitude of striatal dopamine depletion. Regardless of sex, C57BL/6J mice demonstrated approximately 1.4 to 2.2 times greater dopamine depletions in the striatum compared to BALB/c mice. Moreover, methamphetamine caused 4 times greater serotonin depletions in male as opposed to female BALB/c mice while sparing either sex of the C57BL/6J mice. Furthermore, female mice of both strains appeared to have the greatest basal dopamine levels during proestrus and the lowest basal dopamine levels during diestrus. Likewise, female mice of both strains exhibited the lowest dopamine depletions in the striatum when the dosing regimen of methamphetamine started at proestrus whereas the greatest dopamine depletions in the striatum occurred when the regimen started during diestrus. These results suggest that sex hormones and other modulating factors may play a role in methamphetamine-induced dopamine and serotonin neurotoxicity.