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

    David F. Werner, Patrizia Porcu, Kevin N. Boyd, Todd K. O’Buckley, Jenna M. Carter, Sandeep Kumar, A. Leslie Morrow
    TLDR Chronic ethanol increases certain brain receptor levels, influenced by steroids and protein changes.
    The study investigated the regulation of thalamic GABAA receptor α4 subunit expression following acute and chronic ethanol exposure. It was found that a 6-week chronic ethanol diet increased α4 subunit expression, whereas a 2-week exposure did not. Acute high-dose ethanol exposure led to a decrease in α4 subunit levels at 2 hours, followed by a transient increase. These changes were associated with alterations in phosphorylation states and were influenced by neuroactive steroids, as inhibiting steroid production with finasteride prevented the delayed increase in α4 expression. The study highlighted the role of protein kinase C (PKC) and neuroactive steroids in the regulation of these receptors, suggesting that similar mechanisms might be involved in other brain regions.
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