Short-term steroid treatment increases δ GABA A receptor subunit expression in rat CA1 hippocampus: Pharmacological and behavioral effects

Abstract

In this study, 48 h administration of 3α-OH-5β-pregnan-20-one (3α,5β-THP) or 17β-estradiol (E 2)+progesterone (P) to female rats increased expression of the δ subunit of the GABA A receptor (GABAR) in CA1 hippocampus. Coexpression of α4 and δ subunits was suggested by an increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7- tetrahydroisoxazolo[5,4- c]pyridin-3-ol (THIP), following 48 h steroid treatment, and nearly complete blockade by 300 μM lanthanum (La 3+). Because α4βδ GABAR are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice. The La 3+-sensitive THIP current, representative of current gated by α4βδ GABAR, was measurable only following 48 h steroid treatment. In contrast, the bicuculline-sensitive current was not altered by steroid treatment, assessed with or without 200 nM gabazine to block synaptic current. However, 48 h steroid treatment resulted in a tonic current insensitive to the benzodiazepine agonists lorazepam (10 μM) and zolpidem (100 nM). These results suggest that 48 h steroid treatment increases expression of α4βδ GABAR which replace the ambient receptor population. Increased anxiolytic effects of THIP were also observed following 48 h steroid treatment. The findings from the present study may be relevant for alterations in mood and benzodiazepine sensitivity reported across the menstrual cycle.