Expression of ethanol-induced behavioral sensitization is associated with alteration of chromatin remodeling in mice

Ethanol-induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of addiction. EIBS does not occur uniformly in all animals even from the same inbred strain. Since recent data demonstrate that epigenetic mechanisms are likely to be involved in the development a...

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Veröffentlicht in:PloS one 2012-10, Vol.7 (10), p.e47527
Hauptverfasser: Botia, Béatrice, Legastelois, Rémi, Alaux-Cantin, Stéphanie, Naassila, Mickaël
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Naassila, Mickaël
description Ethanol-induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of addiction. EIBS does not occur uniformly in all animals even from the same inbred strain. Since recent data demonstrate that epigenetic mechanisms are likely to be involved in the development and the persistence of ethanol-related behaviors, we explored the involvement of epigenetic mechanisms in ethanol response after EIBS development. DBA/2J mice were i.p. injected with saline or ethanol (2 g/kg) once a day for 10 consecutive days. At day 17, ethanol-treated mice were split in resistant and sensitized groups. Brains were then removed 30 min after a saline or 2 g/kg ethanol challenge to assess i) gene expression using PCR array targeting 84 epigenetic-related genes and ii) histone deacetylases (HDAC), histone acetylases (HAT) and DNA methyltransferases (DNMT) activities as well as H4K12 acetylation. Acute ethanol administration decreased dnmt1, esco2 and rps6ka5 genes expression. These genes were similarly altered in sensitized but not in resistant mice after an ethanol challenge, suggesting that resistant mice were tolerant to the transcriptional outcomes of an ethanol challenge. Whereas global HAT or DNMT activity was not affected, global HDAC activity was reduced after an acute ethanol injection. HDAC inhibition occurred in all ethanol-treated mice but with a lesser extent in sensitized animals. As a consequence, H4 acetylation was specifically potentiated in the core of the Nac proportionally to the striatal HDAC activity decrease. The present study highlights that the contrasted behavioral response to an ethanol challenge between resistant and sensitized mice may be mediated by epigenetic mechanisms occurring specifically in the striatum. Here we show that vulnerability to ethanol dependence and relapse could be, at least in part, due to individual variability in acute ethanol-induced epigenetic response.
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These genes were similarly altered in sensitized but not in resistant mice after an ethanol challenge, suggesting that resistant mice were tolerant to the transcriptional outcomes of an ethanol challenge. Whereas global HAT or DNMT activity was not affected, global HDAC activity was reduced after an acute ethanol injection. HDAC inhibition occurred in all ethanol-treated mice but with a lesser extent in sensitized animals. As a consequence, H4 acetylation was specifically potentiated in the core of the Nac proportionally to the striatal HDAC activity decrease. The present study highlights that the contrasted behavioral response to an ethanol challenge between resistant and sensitized mice may be mediated by epigenetic mechanisms occurring specifically in the striatum. 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EIBS does not occur uniformly in all animals even from the same inbred strain. Since recent data demonstrate that epigenetic mechanisms are likely to be involved in the development and the persistence of ethanol-related behaviors, we explored the involvement of epigenetic mechanisms in ethanol response after EIBS development. DBA/2J mice were i.p. injected with saline or ethanol (2 g/kg) once a day for 10 consecutive days. At day 17, ethanol-treated mice were split in resistant and sensitized groups. Brains were then removed 30 min after a saline or 2 g/kg ethanol challenge to assess i) gene expression using PCR array targeting 84 epigenetic-related genes and ii) histone deacetylases (HDAC), histone acetylases (HAT) and DNA methyltransferases (DNMT) activities as well as H4K12 acetylation. Acute ethanol administration decreased dnmt1, esco2 and rps6ka5 genes expression. These genes were similarly altered in sensitized but not in resistant mice after an ethanol challenge, suggesting that resistant mice were tolerant to the transcriptional outcomes of an ethanol challenge. Whereas global HAT or DNMT activity was not affected, global HDAC activity was reduced after an acute ethanol injection. HDAC inhibition occurred in all ethanol-treated mice but with a lesser extent in sensitized animals. As a consequence, H4 acetylation was specifically potentiated in the core of the Nac proportionally to the striatal HDAC activity decrease. The present study highlights that the contrasted behavioral response to an ethanol challenge between resistant and sensitized mice may be mediated by epigenetic mechanisms occurring specifically in the striatum. Here we show that vulnerability to ethanol dependence and relapse could be, at least in part, due to individual variability in acute ethanol-induced epigenetic response.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23110077</pmid><doi>10.1371/journal.pone.0047527</doi><tpages>e47527</tpages><orcidid>https://orcid.org/0000-0002-9788-0918</orcidid><orcidid>https://orcid.org/0000-0002-7773-5836</orcidid><oa>free_for_read</oa></addata></record>
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subjects Acetylation
Acetylation - drug effects
Addictions
Alcoholism
Animals
Behavior, Animal - drug effects
Biology
Botia
Brain research
Chemistry
Chromatin
Chromatin Assembly and Disassembly - drug effects
Chromatin Assembly and Disassembly - genetics
Chromatin remodeling
Cocaine
Deoxyribonucleic acid
DNA
DNMT1 protein
Dopamine
Drug dependence
Epigenetic inheritance
Epigenetics
Ethanol
Ethanol - metabolism
Ethanol - toxicity
Female
Gene expression
Genes
Genetically modified mice
Health aspects
Histone Acetyltransferases - genetics
Histone deacetylase
Histone Deacetylases - genetics
Histones - drug effects
Histones - metabolism
Inbreeding
Kinases
Life Sciences
Medicine
Methamphetamine
Methyltransferases
Mice
Neostriatum
Neurons and Cognition
Polymerase Chain Reaction
Saline solutions
Transcription
title Expression of ethanol-induced behavioral sensitization is associated with alteration of chromatin remodeling in mice
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