Inhibition of KAR-mediated responses has been observed at quite low EtOH concentrations (Costa et al. 2000; Lack et al. 2008; Valenzuela et al. 1998a; Weiner et al. 1999). However, direct examination of KAR-mediated ion current has yielded mixed results, at least for the receptor constructs examined to date (Dildy-Mayfield and Harris 1992; Valenzuela et al. 1998a). Thus, it is not yet clear whether EtOH inhibition of KAR function involves a direct effect on protein function or a more indirect action. EtOH inhibition of iGluRs is generally thought to dampen neuronal excitability in many brain regions by reducing excitatory synaptic drive and inhibiting synaptic plasticity that requires iGluR activation.
