Adrenalectomy selectively regulates GABAA receptor subunit expression in the hippocampus

Hippocampal function is modulated by adrenal corticosteroids released in a diurnal rhythm or in response to stress. Hippocampal excitability is also modulated by the activity of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain. One mechanism of corticosteroid action in the hippocampus is likely to be via regulation of the GABA system, including corticosteroid regulation of GABAA receptor expression. The GABAA receptor is a heterooligomeric complex composed of subunits derived from a number of distinct genes. We examined the effects of short-term adrenalectomy and low-level corticosterone replacement on mRNA levels for 5 GABAA receptor subunits. In situ hybridization studies demonstrated that mRNA levels for GABAA receptor alpha 1, alpha 2, beta 2, and gamma 2 subunits were altered in the hippocampus of female rats by adrenalectomy. Levels of alpha 1 and gamma 2 mRNA increased in CA3, alpha 2 mRNA increased in the dentate gyrus, while beta 2 mRNA decreased in the dentate gyrus and CA2 relative to sham-operated animals following adrenalectomy. These effects were reversed by the addition of 100 micrograms/ml corticosterone to the drinking water. Adrenalectomy had no effect on the levels of beta 1 mRNA and no effect on any subunit examined in CA1 or the cingulate cortex. These data support the conclusion that corticosteroids can modulate hippocampal excitability through the site-specific regulation of the expression of specific GABAA receptor subunits. Corticosterone-induced changes in subunit expression might alter GABAergic synaptic inhibition by altering the density of GABAA receptors or altering the subunit composition and thereby the pharmacological properties of the receptors.