Chunk #16 — Acute effects of ethanol on GABAA receptors — Direct effects on GABAA receptor subtypes — Low dose effects of ethanol (≤30 mM) on tonic inhibition
In parallel, the ‘ethanol antagonist’ Ro15-4513 has been shown to bind with high affinity to δ-GABAA receptors that are activated by low concentrations of ethanol (Hanchar et al. 2006). Ethanol-induced potentiation of α4βδ-GABAA receptors by low ethanol concentrations is blocked by Ro15-4513 (Wallner et al. 2006). Changes in tonic inhibition may alter ethanol-related behavioral responses. Hanchar et al. (2005) noted that a naturally occurring mutation found in outbred Sprague-Dawley rats (arginine100 to glutamine, R100Q; also found in Sardinian non-preferring rats and ethanol non-tolerant rats) substantially increases the sensitivity of α6β3δ-GABAA receptors to ethanol. Importantly, rats with the naturally occurring mutation exhibit greater enhancement of tonic inhibition in cerebellar granule cells as well as greater motor impairment due to ethanol. Moreover, it now appears that tonic current is not solely dependent on the presence of α4δ- or α6δ-GABAA receptors. α1δ-GABAA receptors also mediate ethanol-induced increases in tonic inhibition in hippocampal interneurons in α4-GABAA receptor knockout mice (Glykys et al. 2007). Further studies of ethanol actions on these receptors are needed.
