Maternal separation increases methamphetamine-induced damage in the striatum in male, but not female rats

• Early life stress increased methamphetamine-induced dopamine damage in the striatum.
• This effect occurred in male separated rats but not females.
• Core body temperatures were increased by methamphetamine in male rats only.
• There was no difference in core body temperature between separated and control males.

Methamphetamine abuse impacts the global economy through costs associated with drug enforcement, emergency room visits, and treatment. Previous research has demonstrated early life stress, such as childhood abuse, increases the likelihood of developing a substance abuse disorder. However, the effects of early life stress on neuronal damage induced by binge methamphetamine administration are unknown. We aimed to elucidate the effects of early life stress on methamphetamine induced dopamine damage in the striatum. Pups were separated from dams for 3 h per day during the first two weeks of development or 15 min for control. In adulthood, rats received either subcutaneous 0.9% saline or 5.0 mg/kg METH injections every 2 h for a total of four injections. Rectal temperatures were taken before the first injection and 1 h after each subsequent injection. Seven days after treatment, rats were euthanized and striatum was collected for quantification of tyrosine hydroxylase (TH) and dopamine transporters (DAT) content by Western blot. Methamphetamine significantly elevated core body temperature in males and decreased striatal DAT and TH content, and this effect was potentiated by early life stress. Females did not exhibit elevated core body temperatures or changes in DAT or TH in either condition. Results indicate maternal separation increases methamphetamine induced damage, and females are less susceptible to methamphetamine induced damage.