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- W2029013359 endingPage "423" @default.
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- W2029013359 abstract "γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the central nervous system and it acts at the GABAA and GABAB receptors. A possible role for the GABAA receptors in alcohol action has been derived from in vitro cell models, animal studies and human research. GABAA subunit mRNA expression in cell models has suggested that the long form of the γ2 subunit is essential for ethanol enhanced potentiation of GABAA receptors, by phosphorylation of a serine contained within the extra eight amino acids. Several animal studies have demonstrated that alterations in drug and alcohol responses may be caused by amino-acid differences at the GABAAα6 and GABAAγ2 subunits. An Arg100/Glu100 change at the GABAAα6 subunit conferring altered binding efficacy of the benzodiazepine inverse agonist Ro 15–4513, was found between the AT (alcohol tolerance) and ANT (alcohol non-tolerance) rats. Several loci related to alcohol withdrawal on mouse chromosome 11 which corresponds to the region containing four GABAA subunit (β2, α6, α1 and γ2) genes on human chromosome 5q33–34, were also identified. Gene knockout studies of the role of GABAAα6 and GABAAγ2 subunit genes in mice have demonstrated an essential role in the modulation of other GABAA subunit expression and the efficacy of benzodiazepine binding. Absence of the GABAAγ2 subunit gene has more severe effects with many of the mice dying shortly after birth. Disappointingly few studies have examined the effects of response to alcohol in these gene knockout mice. Human genetic association studies have suggested that the GABAAβ2, α6, α1 and γ2 subunit genes have a role in the development of alcohol dependence, although their contributions may vary between ethnic group and phenotype. In summary, in vitro cell, animal and human genetic association studies have suggested that the GABAAβ2, α6, α1 and γ2 subunit genes have an important role in alcohol related phenotypes (300 words)." @default.
- W2029013359 created "2016-06-24" @default.
- W2029013359 creator A5019234104 @default.
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- W2029013359 date "2000-11-01" @default.
- W2029013359 modified "2023-10-12" @default.
- W2029013359 title "Role of the GABAAβ2, GABAAα6, GABAAα1 and GABAAγ2 receptor subunit genes cluster in drug responses and the development of alcohol dependence" @default.
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- W2029013359 doi "https://doi.org/10.1016/s0197-0186(00)00054-1" @default.
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