Chronic stress regulates levels of mRNA transcripts encoding β subunits of the GABA A receptor in the rat stress axis

Abstract

Semi-quantitative hybridization histochemical analyses were undertaken to determine expression levels of mRNA transcripts encoding the β1–3 subunits of the GABA Areceptor within the rat hypothalamic paraventricular nucleus (PVN) and hippocampal formation following exposure to a chronic non-habituating stress protocol. After delivery of a battery of stressors on a randomized schedule over a 3-week period, expression levels of the β1 subunit of the GABA A receptor were found to be decreased in the medial parvocellular PVN (mpPVN) by 48.3% relative to control animals. Levels of β2 mRNA following chronic stress were also found to be decreased in the mpPVN (29.8%), but increased in hippocampal subfields CA 1 and CA 3 (33.9 and 23.2%, respectively) and increased (24%) in the dentate gyrus. The results suggest that GABA A receptor subunit composition may be altered at a key regulatory site, and may have important implications for studies aimed at understanding GABAergic inhibitory influences upon the hypothalamic–pituitary–adrenocortical (HPA) axis. Hypophysiotropic CRH neurons serve as the origin of the final common pathway for glucocorticoid secretion in response to stressful stimuli, and GABAergic afferents have been implicated in afferent control of these neurons. Regulation of GABA A receptors at these sites may alter the efficacy of a major inhibitory influence upon the stress axis, and thereby modulate stress-induced glucocorticoid secretion.