Sex differences in memory and intracellular signaling after methamphetamine binge treatment

Methamphetamine is a neurotoxic psychostimulant known to cause cell death and terminal degradation of dopaminergic neurons in the striatum concomitant with memory deficits. However, most of the research studies have not examined the influence of sex on these changes. In this study we compared the effects of a binge regimen of methamphetamine (four injections of 4 mg/kg) on male, female, and ovariectomized (OVX) female Sprague-Dawley rats. We show that male and OVX female animals had a deficit in a novel object recognition task, while intact females did not show this deficit. Neurochemical analysis of the same animals indicated higher levels of FosB protein in caudate-putamen (CPu) and nucleus accumbens (NAc) of the male animals than intact or OVX females. Methamphetamine also increased Bcl-2 protein levels in CPu of all the cohorts. We did not find a significant effect of methamphetamine on the dopamine neuron markers tyrosine hydroxylase (TH) or dopamine transporter (DAT) 7 days after methamphetamine administrations. Our behavioral and neurochemical studies indicate that methamphetamine differentially affects male and female animals and shows sex differences in memory and molecular mechanisms in the striatum of these animals.