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Antibodies Specific for GABA A Receptor α Subunits Reveal that Chronic Alcohol Treatment Down‐Regulates α‐Subunit Expression in Rat Brain Regions
Author(s) -
Mhatre Molina C.,
Pena Gina,
Sieghart Werner,
Ticku Maharaj K.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb09795.x
Subject(s) - protein subunit , receptor , cerebral cortex , gabaergic , cerebellum , long term potentiation , medicine , endocrinology , biology , chemistry , biochemistry , gene
— 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 GABA A receptor‐mediated 36 Cl − uptake in cortical synaptoneurosomes and primary cultured neurons. We and others have shown that it also results in a 40‐50% reduction in GABA A receptor α‐subunit mRNA levels in the rat cerebral cortex. In the present study, we investigated the expression of α 1 , α 2 , and α 3 subunits of the GABA A receptor in the cerebral cortex and the α 1 subunit in the cerebellum by immunoblotting using polyclonal antibodies raised against α 1 ‐, α 2 ‐, and α 3 ‐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 GABA A receptor α 1 subunit (51 kDa), 47 ± 8% reduction in level of the α 2 subunit (53 kDa), and 30 ± 7% reduction in level of the α 3 subunit (59 kDa) in the cerebral cortex and a 56 ± 5% reduction in content of the α 1 subunit in the cerebellum. In summary, this ethanol‐induced reduction in content of the GABA A receptor α subunits may underlie alterations in the GABA A receptor function and could be related to cellular adaptation to the functional disturbance caused by ethanol.