Ethanol administration rapidly reverses alpha4 GABAA receptor subunit upregulation following steroid exposure.
Both short-term (48 h) exposure to the neuroactive steroid 3alpha,5alpha[beta]-THP and its withdrawal increase expression of the benzodiazepine (BDZ)-insensitive GABAA receptor (GABAR) alpha4 subunit in hippocampus. This increase in alpha4 subunit expression was associated with a relative insensitivity of CA1 hippocampal pyramidal cells to modulation of GABA-gated current by the BDZ lorazepam (LZM), assessed using whole cell patch clamp techniques. Chronic ethanol is also known to regulate expression of the alpha4 subunit. Thus, in the present study we investigated the capacity of ethanol, administered in low doses across a 2 h period (0.5 g/kg, i.p., 3x), to suppress alpha4 expression produced by 48 h exposure to 3alpha,5 beta-THP in adult female rats. We show here that 2 h ethanol administration reverses the increase in alpha4 expression normally observed following 48 h steroid treatment. This effect was correlated with a recovery of responses recorded from CA1 hippocampal pyramidal cells to the GABA-modulatory effects of LZM. Similar effects of ethanol in suppressing alpha4 expression and restoring LZM responsiveness were seen following steroid withdrawal when alpha4 expression is normally increased. These results suggest that increases in expression of the alpha4 subunit produced by steroid exposure or withdrawal are altered by other GABA-modulatory drugs, such as ethanol.
Smith
Sheryl S
SS
Department of Physiology and Pharmacology, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. sheryl.smith@downstate.edu
Gong
Qi Hua
QH
D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008297:Male; D018408:Patch-Clamp Techniques; D021122:Protein Subunits / Q000235:genetics; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000235:genetics*; D013256:Steroids / Q000494:pharmacology*
D021122:Protein Subunits; D011963:Receptors, GABA-A; D013256:Steroids; D000431:Ethanol