Dopamine transporter function differences between male and female CD-1 mice.

It has been reported that male mice are more susceptible to the neurotoxic effects of methamphetamine (MA) upon the nigrostriatal dopaminergic (NSDA) system. Since MA utilizes the dopamine transporter (DAT) to exert its effects, in the present study, we tested for differences in the dynamics of DAT function between male and female mice as an approach to understand some of the bases for this sex difference in MA-induced NSDA neurotoxicity. To accomplish this goal, in Experiment 1, the amount of dopamine (DA) obtained following DA infusion into the superfused striatal tissue fragments of male and female mice was measured while in Experiment 2 responses to the DA uptake blocker, nomifensine (NMF), were assessed in these preparations. The differences obtained to these treatments demonstrate that marked differences in DA transporter activity exist between male and female mice. When combining the DA and DOPAC measures from these two experiments, the data suggest that the female mice show a more active and efficient recovery and vesicular packaging of extracellular DA. These findings have important implications for sex differences in NSDA functions and responses to neurotoxins which enter the neurons via the DAT.