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GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Naïve P and NP Rats (Hippocampal GABAergic Gene Expression in Addiction)

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 neuron... Full description

Journal Title: PLoS ONE 2012, Vol.7(1), p.e29369
Main Author: Enoch, Mary-Anne
Other Authors: Zhou, Zhifeng , Kimura, Mitsuru , Mash, Deborah C , Yuan, Qiaoping , Goldman, David
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0029369
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recordid: plos10.1371/journal.pone.0029369
title: GABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Naïve P and NP Rats (Hippocampal GABAergic Gene Expression in Addiction)
format: Article
creator:
  • Enoch, Mary-Anne
  • Zhou, Zhifeng
  • Kimura, Mitsuru
  • Mash, Deborah C
  • Yuan, Qiaoping
  • Goldman, David
subjects:
  • Research Article
  • Biology
  • Medicine
  • Genetics And Genomics
  • Neuroscience
  • Pharmacology
  • Biochemistry
ispartof: PLoS ONE, 2012, Vol.7(1), p.e29369
description: 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. ; Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, 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. ; Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10, 7×10 respectively). Principal FDR-corrected findings were that was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in , implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. , encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with , encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (, ), alcoholics () and P rats (, ). ; Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0029369
fulltext: fulltext
issn:
  • 1932-6203
  • 19326203
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titleGABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Naïve P and NP Rats (Hippocampal GABAergic Gene Expression in Addiction)
creatorEnoch, Mary-Anne ; Zhou, Zhifeng ; Kimura, Mitsuru ; Mash, Deborah C ; Yuan, Qiaoping ; Goldman, David
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subjectResearch Article ; Biology ; Medicine ; Genetics And Genomics ; Neuroscience ; Pharmacology ; Biochemistry
descriptionBy 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. ; Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, 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. ; Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10, 7×10 respectively). Principal FDR-corrected findings were that was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in , implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. , encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with , encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (, ), alcoholics () and P rats (, ). ; Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications.
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titleGABAergic Gene Expression in Postmortem Hippocampus from Alcoholics and Cocaine Addicts; Corresponding Findings in Alcohol-Naïve P and NP Rats (Hippocampal GABAergic Gene Expression in Addiction)
descriptionBy 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. ; Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, 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. ; Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10, 7×10 respectively). Principal FDR-corrected findings were that was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in , implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. , encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with , encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (, ), alcoholics () and P rats (, ). ; Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications.
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abstractBy 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. ; Using RNA-Seq we quantified mRNA transcripts in postmortem total hippocampus from alcoholics, cocaine addicts and controls and also from alcohol-naïve, 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. ; Directionally consistent and biologically plausible overlapping and specific changes were detected: 14/25 of the human genes and 12/25 of the rat genes showed nominally significant differences in gene expression (global p values: 9×10, 7×10 respectively). Principal FDR-corrected findings were that was down-regulated in alcoholics, cocaine addicts and P rats with congruent findings in , implicated in GABAB signaling efficacy, potentially resulting in increased synaptic GABA. , encoding the gamma2 subunit required for postsynaptic clustering of GABAA receptors together with , encoding the associated scaffolding protein gephryin, were both down-regulated in alcoholics and cocaine addicts but were both up-regulated in P rats. There were also expression changes specific to cocaine addicts (, ), alcoholics () and P rats (, ). ; Our study confirms the involvement of the GABAergic system in alcoholism but also reveals a hippocampal GABA input in cocaine addiction. Congruent findings in human addicts and P rats provide clues to predisposing factors for alcohol and drug addiction. Finally, the results of this study have therapeutic implications.
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