Low doses of ethanol and a neuroactive steriod positively interact to modulate rat GABA_A receptor function

Fast inhibitory responses in the central nervous system are mediated by the GABA_A receptor. The activation and function of the GABA_A receptor can be modulated by a variety of compounds including benzodiazepines, barbiturates and neuroactive steroids. Modulation of the GABA_A receptor function by ethanol has been observed in some but not all studies. We have studied the effect of ethanol at concentrations corresponding to light intoxication on the function of the recombinant GABA_A receptor containing α1β2γ2 subunits. The experiments were performed both in the absence and presence of low, subthreshold concentrations of a neuroactive steroid. The results demonstrate that, in the presence of the steroid, 0.05 % (9 mM) ethanol potentiates the GABA_A receptor function by increasing the channel mean open duration. No effect was observed on the channel closed time durations. The data suggest that ethanol influences channel closing with no effect on the affinity of the receptor for GABA or the channel opening rate constant.