GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Na？ve P and NP Rats 英文参考文献.docVIP

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GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Na？ve P and NP Rats 英文参考文献.doc

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GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Na？ve P and NP Rats 英文参考文献

GABAergicGeneExpressioninPostmortem HippocampusfromAlcoholicsandCocaineAddicts; CorrespondingFindingsinAlcohol-Na?¨vePandNPRats Mary-AnneEnoch1*,ZhifengZhou1,MitsuruKimura1,DeborahC.Mash2,QiaopingYuan1 ,David Goldman1 1NationalInstituteonAlcoholAbuseandAlcoholism, NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica, 2SchoolofMedicine,Universityof Miami,Miami,Florida,UnitedStatesofAmerica Abstract Background: By performing identical studies in humans and rats, we attempted to distinguish vulnerability factors for addiction from neurobiological effects of chronic drug exposure. We focused on the GABAergic system within the hippocampus, a brain region that is a constituent of the memory/conditioning neuronal circuitry of addiction that is consideredtobeimportantindrugreinforcementbehaviorsinanimalsandcravingandrelapseinhumans. Methodology:UsingRNA-SeqwequantifiedmRNAtranscriptsinpostmortemtotalhippocampusfromalcoholics,cocaine addicts and controls and also from alcohol-na?¨ve, alcohol preferring (P) and non-preferring (NP) rats selectively bred for extremes of alcohol-seeking behavior that also show a general addictive tendency. A pathway-targeted analysis of 25 GABAergicgenesencodingproteinsimplicatedinGABAsynthesis,metabolism, synaptictransmissionandre-uptakewas undertaken. PrincipalFindings:Directionallyconsistentandbiologicallyplausibleoverlappingandspecificchangesweredetected:14/ 25ofthehumangenesand12/25oftheratgenesshowednominallysignificantdifferencesingeneexpression(globalp values: 9610214, 7610211 respectively). Principal FDR-corrected findings were that GABBR1 was down-regulated in alcoholics,cocaineaddictsandPratswithcongruentfindingsinNSF,implicatedinGABABsignalingefficacy,potentially resulting in increased synaptic GABA. GABRG2, encoding the gamma2 subunit required for postsynaptic clustering of GABAAreceptorstogetherwithGPHN,encodingtheassociatedscaffoldingproteingephryin,werebothdown-regulatedin alcoholicsandcocaineaddictsbu