Following chronic ethanol administration, there are specific adaptations of GABAA receptors that appear to mediate increased CNS excitability. These mechanisms could be targeted for therapeutic benefits. However, there are many unanswered questions in this realm as well. What is the significance of changes in α2-, α3-, β2-, β3-, and γ1-GABAA receptors? Can we modulate PKC and PKA interactions with GABAA receptors selectively? Would effects of these protein kinases on other ion channels interfere with therapeutic strategies for modulation of GABAA receptors? Can we target specific phosphorylation sites on specific proteins? Would this interfere with the actions of other endogenous modulators?
