biostudies-literature00550Trudell JRNIAAA NIH HHS317-23https://www.ebi.ac.uk/biostudies/studies/S-EPMC4089033biostudies-literatureUnknown35(7)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.Trends in pharmacological sciencesAlcohol dependence: molecular and behavioral evidence.PMC4089033R01AA013378AA017072U01 AA013520R01 AA006399R01 AA013588P50 AA017072R01 AA012404R37 AA013588AA06399R37 AA006399R01 AA020980R01 AA013378AA018316AA013588Harris RAMayfield JMessing ROTrudell JR55falseAlcohol dependence: molecular and behavioral evidence.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.2014-01-01T00:00:00Z2014 Jul2024-11-13T05:45:20.143Z2019-06-06T13:00:14ZS-EPMC40890332486594410.1016/j.tips.2014.04.009