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

In this study, 48 h administration of 3 alpha-OH-5 beta-pregnan-20-one (3 alpha,5 beta-THP) or 17 beta-estradiol (E-2)+progesterone (P) to female rats increased expression of the delta subunit of the GABA(A) receptor (GABAR) in CA1 hippocampus. Coexpression of alpha 4 and delta 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 mu M lanthanum (La3+). Because alpha 4 beta delta GABAR are extrasynaptic, we also recorded pharmacologically isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the slice. The La3+-sensitive THIP current, representative of current gated by alpha 4 beta delta 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 mu M) and zolpidem (100 nM). These results suggest that 48 h steroid treatment increases expression of alpha 4 beta delta 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. (c) 2005 Elsevier Ltd. All rights reserved.