Ethanol effects on GABA-gated current in a model of increased α4βδ GABAA receptor expression depend on time course and preexposure to low concentrations of the drug

Abstract Several recent studies have suggested that αβδ subtypes of γ-aminobutyric acid type A (GABA A ) receptors (δ-GABAR) are a target for low dose ethanol ( 20 )-gated current was recorded with whole-cell patch clamp procedures from acutely isolated pyramidal cells. We assessed ethanol's effect on GABA-gated current using either (1) 2–5 min application of ethanol in increasing concentrations (0.1–30 mM) or (2) coadministration of ethanol with GABA. Two minute application of 1–3 mM ethanol produced optimal potentiation of GABA-gated current following steroid treatment, with higher concentrations less effective. In contrast, 30 mM ethanol produced optimal effects when ethanol was not preapplied. However, following preapplication of 1 mM ethanol, 30 mM ethanol decreased the peak GABA-gated current. These findings suggest that ethanol may act at multiple interacting sites to affect GABAR efficacy and desensitization. These data also suggest that ethanol effects on GABA-gated current are affected by the time course of exposure and previous exposure to low concentrations of the drug.