Antibodies Specific for GABAA Receptor α Subunits Reveal that Chronic Alcohol Treatment Down‐Regulates α‐Subunit Expression in Rat Brain Regions

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Abstract
— Chronic administration of ethanol results in the development of tolerance and dependence. The molecular mechanism underlying these behavioral actions of ethanol is poorly understood. Several lines of evidence have suggested that some of the pharmacological actions of ethanol are mediated via a potentiation of GABAergic transmission. Chronic ethanol administration results in a reduction in the GABAA receptor-mediated 36Cl− uptake in cortical synaptoneurosomes and primary cultured neurons. We and others have shown that it also results in a 40-50% reduction in GABAA receptor α-subunit mRNA levels in the rat cerebral cortex. In the present study, we investigated the expression of α1, α2, and α3 subunits of the GABAA receptor in the cerebral cortex and the α1 subunit in the cerebellum by immunoblotting using polyclonal antibodies raised against α1-, α2-, and α3-subunit polypeptides following chronic ethanol treatment. These results reveal that chronic ethanol administration to rats results in a 61 ± 4% reduction in level of the GABAA receptor α1subunit (51 kDa), 47 ± 8% reduction in level of the α2subunit (53 kDa), and 30 ± 7% reduction in level of the α3subunit (59 kDa) in the cerebral cortex and a 56 ± 5% reduction in content of the α1 subunit in the cerebellum. In summary, this ethanol-induced reduction in content of the GABAA receptor α subunits may underlie alterations in the GABAA receptor function and could be related to cellular adaptation to the functional disturbance caused by ethanol.