Adrenalectomy selectively regulates gaba_a 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 γ-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 GABA_A receptor expression. The GABA_A 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 GABA_A receptor subunits. In situ hybridization studies demonstrated that mRNA levels for GABA_A receptor α1, α2, β2, and γ2 subunits were altered in the hippocampus of female rats by adrenalectomy. Levels of α1 and γ2 mRNA increased in CA3, α2 mRNA increased in the dentate gyrus, while β2 mRNA decreased in the dentate gyrus and CA2 relative to sham-operated animals following adrenalectomy. These effects were reversed by the addition of 100 μg/ml corticosterone to the drinking water. Adrenalectomy had no effect on the levels of β1 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 GABA_A receptor subunits. Corticosterone-induced changes in subunit expression might alter GABAergic synaptic inhibition by altering the density of GABA_A receptors or altering the subunit composition and thereby the pharmacological properties of the receptors.