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Chronic Ethanol Administration Regulates the Expression of GABA A Receptor α 1 and α 5 Subunits in the Ventral Tegmental Area and Hippocampus
Author(s) -
Charlton Maura E.,
Sweetnam Paul M.,
Fitzgerald Lawrence W.,
Terwilliger Rosemarie Z.,
Nestler Eric J.,
Duman Ronald S.
Publication year - 1997
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 - 10.1046/j.1471-4159.1997.68010121.x
Subject(s) - ventral tegmental area , hippocampus , gabaa receptor , hippocampal formation , neuroscience , medicine , protein subunit , gabaergic , endocrinology , cerebellum , receptor , biology , chemistry , biochemistry , dopamine , dopaminergic , gene
Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABA A receptors throughout the CNS. Conceivably, changes in receptor function may be associated with alterations of subunit composition. In the present study, a comprehensive (1–12 weeks) ethanol treatment paradigm was used to evaluate changes in GABA A receptor subunit expression in several brain regions including the cerebellum, cerebral cortex, ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and the hippocampus (a region involved in memory/cognition). Expression of α 1 and α 5 subunits was regulated by ethanol in a region‐specific and time‐dependent manner. Following 2–4 weeks of administration, cortical and cerebellar α 1 and α 5 subunit immunoreactivity was reduced. In the VTA, levels of α 1 subunit immunoreactivity were significantly decreased after 12 weeks but not 1–4 weeks of treatment. Hippocampal α 1 subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast, α 5 mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABA A receptor subunit expression in the VTA and hippocampus, effects that may play a role in the abuse potential and detrimental cognitive effects of alcohol.