title: Alcohol dependence: molecular and behavioral evidence.
abstract: Alcohol dependence is a complex condition with clear genetic factors. Some of the leading candidate genes code for subunits of the inhibitory GABAA and glycine receptors. These and related ion channels are also targets for the acute actions of alcohol, and there is considerable progress in understanding interactions of alcohol with these proteins at the molecular and even atomic levels. X-ray structures of open and closed states of ion channels combined with structural modeling and site-directed mutagenesis have elucidated direct actions of alcohol. Alcohol also alters channel function by translational and post-translational mechanisms, including phosphorylation and protein trafficking. Construction of mutant mice with either deletion of key proteins or introduction of alcohol-resistant channels has further linked specific proteins with discrete behavioral effects of alcohol. A combination of approaches, including genome wide association studies in humans, continues to advance the molecular basis of alcohol action on receptor structure and function.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Trudell
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Jody
authors.initials: J
authors.lastname: Mayfield
authors.affiliation: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: harris@austin.utexas.edu.
authors.forename: R Adron
authors.initials: RA
authors.lastname: Harris
mesh_terms: D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D051379:Mice
chemical_list: D007473:Ion Channels; D000431:Ethanol
keywords: GABA(A); GLIC; LGICs; NMDA; PKC; behavior; chronic alcohol consumption; crystal structures; ethanol; gene expression; glycine; knockin mice; knockout; trafficking