gabaergic gene expression in postmortem hippocampus from alcoholics and cocaine addicts; corresponding findings in alcohol-na?ve p and np ratsgaba ergic基因表达在后期海马体酗酒者和可卡因成瘾者;.pdfVIP
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gabaergic gene expression in postmortem hippocampus from alcoholics and cocaine addicts; corresponding findings in alcohol-na?ve p and np ratsgaba ergic基因表达在后期海马体酗酒者和可卡因成瘾者;
GABAergic Gene Expression in Postmortem
Hippocampus from Alcoholics and Cocaine Addicts;
¨
Corresponding Findings in Alcohol-Naıve P and NP Rats
1 1 1 2 1
Mary-Anne Enoch *, Zhifeng Zhou , Mitsuru Kimura , Deborah C. Mash , Qiaoping Yuan , David
Goldman1
1 National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, United States of America, 2 School of Medicine, University of
Miami, Miami, Florida, United States of America
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
considered to be important in drug reinforcement behaviors in animals and craving and relapse in humans.
Methodology: Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine
¨
addicts and controls and also from alcohol-naıve, 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
GABAergic genes encoding proteins implicated in GABA synthesis, metabolism, synaptic transmission and re-uptake was
undertaken.
Principal Findings: Directionally consistent and biologically plausible overlapping and specific changes w
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