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 subs tantial striatal dopamine depletion in both sexes of BALB/c and C57BL/6J mi ce. Male C57BL/6J mice exhibited greater dopamine depletions in the striatu m compared to female C57BL/6J mice. In contrast, male and female BALB/c mic e demonstrated an equivalent magnitude of striatal dopamine depletion. Rega rdless of sex, C57BL/6J mice demonstrated approximately 1.4 to 2.2 times gr eater dopamine depletions in the striatum compared to BALB/c mice. Moreover , methamphetamine caused 4 times greater serotonin depletions in male as op posed 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 basa l dopamine levels during proestrus and the lowest basal dopamine levels dur ing diestrus. Likewise, female mice of both strains exhibited the lowest do pamine depletions in the striatum when the dosing regimen of methamphetamin e started at proestrus whereas the greatest dopamine depletions in the stri atum occurred when the regimen started during diestrus. These results sugge st that sex hormones and other modulating factors may play a role in metham phetamine-induced dopamine and serotonin neurotoxicity.