Analysis of striatum and brain levels reveals sex differences in conversion of methamphetamine to amphetamine in mice.

ABSTRACT

The aim of this study was to compare methamphetamine (Meth) and amphetamine (Amph) levels in the brain of male and female mice. Meth and Amph levels were significantly higher at 30 min after systemic administration of 2 mg/kg of Meth than at 120 min. Meth levels were similar in striatum as in the rest of the brain and there was no sex difference. However, females showed significantly higher levels of Amph compared to males in both regions. The ratio of Amph to Meth levels was significantly higher in female mice than in males at 120 min after Meth administration. In a separate cohort of mice, treatment with 3 mg/kg of Meth induced significant locomotor hyperactivity which was maximum in the first 60 min after injection and not different between male and female mice. Treatment with 1 mg/kg Meth induced mild hyperactivation in female, but not male mice at 60-120 min post-injection. These data show sex differences in conversion of Meth to Amph in mice, which could play a role in sex differences in the behavioural, addictive and neurotoxic properties of Meth in rodents as well as in humans.