Chronic stress regulates levels of mRNA transcripts encoding beta subunitsof the GABA(A) receptor in the rat stress axis

Semi-quantitative hybridization histochemical analyses were undertaken to d etermine expression levels of mRNA transcripts encoding the beta1-3 subunit s of the GABA(A) receptor within the rat hypothalamic paraventricular nucle us (PVN) and hippocampal formation following exposure to a chronic non-habi tuating stress protocol. After delivery of a battery of stressors on a rand omized schedule over a 3-week period, expression levels of the pi subunit o f the GABA(A) receptor were found to be decreased in the medial parvocellul ar PVN (mpPVN) by 48.3% relative to control animals. Levels of beta2 mRNA f ollowing chronic stress were also found to be decreased in the mpPVN (29.8% ), bur 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 regulato ry site, and may have important implications for studies aimed at understan ding GABAergic inhibitory influences upon the hypothalamic-pituitary-adreno -cortical (HPA) axis. Hypophysiotropic CRH neurons serve as the origin of t he final common pathway for glucocorticoid secretion in response to stressf ul stimuli, and GABAergic afferents have been implicated in afferent contro l of these neurons. Regulation of GABA(A) receptors at these sites may alte r the efficacy of a major inhibitory influence upon the stress axis, and th ereby modulate stress-induced glucocorticoid secretion. (C) 2000 Elsevier S cience B.V. All rights reserved.