Chunk #18 — Acute effects of ethanol on GABAA receptors — Direct effects on GABAA receptor subtypes — High dose effects of ethanol (>30 mM) on tonic inhibition
receptor pentamer. However, Kaur et al. (2009) have shown that 30 mM ethanol did not display potentiation in concatenated α1β3δ receptors. In agreement with the lack of a low dose effect, autoradiographic experiments also suggest that Ro15-4513 binding is not altered by low concentrations of ethanol (Korpi et al. 2007). Additionally, the naturally occurring R100Q mutation in α6-GABAA receptors does not increase ethanol sensitivity at extrasynaptic receptors in outbred rats or in ethanol non-tolerant rats as described above (Botta et al. 2007a; Valenzuela et al. 2005). In agreement with the lack of a low dose effect, α4- and δ-GABAA receptor knockout mice do not show any major changes in acute ethanol-related behaviors (Chandra et al. 2008; Mihalek et al. 2001). Nonetheless, electrophysiologic studies utilizing α4-GABAA receptor subunit knockout mice did not show ethanol-enhanced tonic inhibition compared to controls at 50 mM (Jia et al. 2008a; Liang et al. 2008). Many of these studies assessing low dose ethanol effects on extrasynaptic receptors and tonic inhibition are summarized in Table 1.
