-Hydroxybutyric Acid and Diazepam Antagonize a Rapid Increase in GABAA Receptors 4 Subunit mRNA Abundance Induced by Ethanol Withdrawal in Cerebellar Granule Cells

Both benzodiazepines and -hydroxybutyric acid (GHB) are used to treat alcohol withdrawal syndrome. The molecular ba-sis for this therapeutic efficacy was investigated with primary cultures of rat cerebellar granule cells. Long-term exposure of these cells to ethanol (100 mM, 5 days) reduced the abundance of mRNAs encoding the 2L and 2S subunits of the GABA type A receptor (32 and 23%, respectively) but failed to affect that of 1, 4, or 6 subunit mRNAs. Subsequent ethanol with-drawal resulted in decreases in the amounts of 1 (29%), 6 (27%), 2L (64%), and 2S (76%),subunit mRNAs that were maximal after 6 to 12 h. In contrast, 3 h after ethanol withdrawal, the abundance of the 4 subunit mRNA was in-creased by 46%. Ethanol withdrawal did not affect neuronal morphology but reduced cellular metabolic activity. The in