Anabolic androgenic steroids induce age-, sex-, and dose-dependent changes in GABA(A) receptor subunit mRNAs in the mouse forebrain

Abstract

Chronic exposure to anabolic androgenic steroids (AAS) has deleterious effects on reproductive health in both human and animal subjects. Neurotransmission mediated by the gamma-aminobutyric acid type A (GABA(A)) receptor in the medial amygdala (MeA), the medial preoptic area (mPOA), and the ventromedial nucleus (VMN) of the hypothalamus plays a critical role in mediating sexual behaviors. Here we used semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) to examine levels of alpha(1), alpha(2), alpha(5), gamma(1), gamma(2), and epsilon subunit mRNAs in these three regions of the brain. Our results demonstrate that chronic exposure to either a high or a moderate dose of the AAS, 17alpha-methyltestosterone (17alpha-MeT), significantly decreased the levels of specific alpha and gamma subunit mRNAs in a manner that depended on the dose of AAS and age and sex of the animals. Specifically, the moderate dose of AAS elicited significant changes only in pubertal females and the majority of changes observed in pubertal animals with the high dose also occurred in females. In contrast, the moderate dose of AAS induced no significant changes in adult mice of either sex, while the high dose had effects in both males and females. In addition to determining the effects of chronic AAS treatment, a developmental analysis of drug-naïve animals demonstrated that GABA(A) receptor subunit mRNA levels in these regions of the forebrain undergo significant changes as animals proceed through puberty. These data demonstrate that the effects of AAS exposure on GABA(A) receptor expression are superimposed upon dynamic developmental changes that accompany the transition from puberty to adulthood.