Chronic ethanol exposure selectively increases the internalization of α1-GABAA receptors into clathrin-coated vesicles of the cerebral cortex with a corresponding decrease in these receptors in the synaptic fraction (Kumar et al. 2003). In contrast, there is no change in the internalization of α4-GABAA receptors into clathrin-coated vesicles although there is a significant increase in α4 subunit peptide in the synaptic fraction following chronic ethanol exposure. Hence, the regulation of intracellular trafficking following chronic ethanol exposure appears to alter the subtypes of GABAA receptors on the cell surface. This may account for alterations in the pharmacological properties of GABAA receptors that have been observed. Internalization of GABAA receptors following chronic ethanol administration is mediated by clathrin and the adaptor complex (AP) since the association of adaptin-α and clathrin with α1-GABAA receptors in the intracellular fraction was increased following chronic ethanol administration (Kumar et al. 2003). GABAA receptor β2 and/or γ2 subunits are required for recognition of the receptor by the AP-2 that precedes clathrin-dependent endocytosis (Herring et al. 2003; Kittler et al. 2005, 2008). Therefore, it is possible that PKC-mediated phosphorylation
