Chronic exposure to stress levels of corticosterone alters GABA_A receptor subunit mRNA levels in rat hippocampus

Chronic exposure to stress levels of corticosteroids alters many aspects of hippocampal function and may lead to neurodegeneration. Male rats were treated for 10 days with corticosterone (CORT) or vehicle pellets, and mRNA levels for six γ-aminobutyric acid (GABA_A) receptor subunits were measured. Effects of castration on subunit mRNA levels in CORT- and vehicle-treated animals were also examined. In situ hybridization studies demonstrated that mRNA levels for hippocampal GABA_A receptor α1, α2, β1, β2, β3, and γ2 subunits were differentially altered by CORT treatment. Levels of α1 and α2 mRNA decreased in the dentate gyrus, and β1 mRNA levels decreased in CA1 and dentate gyrus of CORT-, compared to vehicle-treated, animals. In contrast, β2 subunit levels increased in all hippocampal regions examined, β3 levels increased in the dentate gyrus, and γ2 levels increased in CA1-CA3. The α1, β1, and β2 mRNA levels all increased in the cingulate cortex of CORT-treated animals. There was no significant effect of gonadal state on any of the subunits examined, but there was a significant negative correlation between testosterone levels and mRNA levels of α1, α2, and β3 in specific regions. These data demonstrate that chronic exposure to stress levels of CORT produces complex changes in the mRNA levels of multiple GABA_A receptor subunits, independently of the CORT-induced suppression of circulating testosterone.