Ethanol-Induced GABAA Receptor Alpha4 Subunit Plasticity Involves Phosphorylation and Neuroactive Steroids

The study investigated the regulation of GABAA receptor α4 subunits in the thalamus following ethanol exposure. It found that chronic ethanol consumption for 6 weeks increased α4 subunit levels, while a 2-week exposure did not. After acute high-dose ethanol administration, α4 subunit levels initially decreased at 2 hours, then transiently increased. These changes were linked to PKCγ and PKCδ levels and serine phosphorylation. The delayed increase in α4 expression was not due to phosphorylation changes but was inhibited by finasteride, indicating a role for neuroactive steroids. The findings suggested that thalamic α4 subunit regulation by ethanol is similar to other brain regions and involves phosphorylation and neuroactive steroids.