Inhibition of DNA methyltransferases regulates cocaine self-administration by rats: a genome-wide DNA methylation study.
Identifieur interne : 000B97 ( Main/Exploration ); précédent : 000B96; suivant : 000B98Inhibition of DNA methyltransferases regulates cocaine self-administration by rats: a genome-wide DNA methylation study.
Auteurs : M. Fonteneau [France] ; D. Filliol [France] ; P. Anglard [France] ; K. Befort [France] ; P. Romieu [France] ; J. Zwiller [France]Source :
- Genes, brain, and behavior [ 1601-183X ] ; 2017.
Descripteurs français
- KwdFr :
- ADN (génétique), Animaux (MeSH), Antienzymes (pharmacologie), Autoadministration (MeSH), Azacitidine (analogues et dérivés), Azacitidine (pharmacologie), Cocaïne (administration et posologie), Cytidine (analogues et dérivés), Cytidine (pharmacologie), DNA modification methylases (antagonistes et inhibiteurs), DNA modification methylases (métabolisme), Décitabine (MeSH), Encéphale (métabolisme), Génome (MeSH), Ilots CpG (MeSH), Mâle (MeSH), Méthylation de l'ADN (MeSH), Phosphatidylinositol 3-kinases (métabolisme), Rat Wistar (MeSH), Rats (MeSH), Régions promotrices (génétique) (MeSH), Troubles liés à la cocaïne (enzymologie), Troubles liés à la cocaïne (génétique), Troubles liés à la cocaïne (métabolisme), Épigenèse génétique (MeSH).
- MESH :
- administration et posologie : Cocaïne.
- analogues et dérivés : Azacitidine, Cytidine.
- antagonistes et inhibiteurs : DNA modification methylases.
- enzymologie : Troubles liés à la cocaïne.
- génétique : ADN, Troubles liés à la cocaïne.
- métabolisme : DNA modification methylases, Encéphale, Phosphatidylinositol 3-kinases, Troubles liés à la cocaïne.
- pharmacologie : Antienzymes, Azacitidine, Cytidine.
- Animaux, Autoadministration, Décitabine, Génome, Ilots CpG, Mâle, Méthylation de l'ADN, Rat Wistar, Rats, Régions promotrices (génétique), Épigenèse génétique.
English descriptors
- KwdEn :
- Animals (MeSH), Azacitidine (analogs & derivatives), Azacitidine (pharmacology), Brain (metabolism), Cocaine (administration & dosage), Cocaine-Related Disorders (enzymology), Cocaine-Related Disorders (genetics), Cocaine-Related Disorders (metabolism), CpG Islands (MeSH), Cytidine (analogs & derivatives), Cytidine (pharmacology), DNA (genetics), DNA Methylation (MeSH), DNA Modification Methylases (antagonists & inhibitors), DNA Modification Methylases (metabolism), Decitabine (MeSH), Enzyme Inhibitors (pharmacology), Epigenesis, Genetic (MeSH), Genome (MeSH), Male (MeSH), Phosphatidylinositol 3-Kinases (metabolism), Promoter Regions, Genetic (MeSH), Rats (MeSH), Rats, Wistar (MeSH), Reinforcement, Psychology (MeSH), Self Administration (MeSH).
- MESH :
- chemical , administration & dosage : Cocaine.
- chemical , analogs & derivatives : Azacitidine, Cytidine.
- chemical , antagonists & inhibitors : DNA Modification Methylases.
- chemical , genetics : DNA.
- chemical , metabolism : DNA Modification Methylases.
- chemical , pharmacology : Azacitidine, Cytidine, Enzyme Inhibitors.
- enzymology : Cocaine-Related Disorders.
- genetics : Cocaine-Related Disorders.
- metabolism : Brain, Cocaine-Related Disorders, Phosphatidylinositol 3-Kinases.
- Animals, CpG Islands, DNA Methylation, Decitabine, Epigenesis, Genetic, Genome, Male, Promoter Regions, Genetic, Rats, Rats, Wistar, Reinforcement, Psychology, Self Administration.
Abstract
DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine (dAZA) and zebularine enhanced the reinforcing properties of cocaine. To obtain some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated with or without dAZA. The study identified nearly 189 000 differentially methylated regions (DMRs), about half of them were located inside gene bodies, while only 9% of DMRs were found in the promoter regions of genes. About 99% of methylation changes occurred outside CpG islands. Gene expression studies confirmed the inverse correlation usually observed between increased methylation and transcriptional activation when methylation occurs in the gene promoter. This inverse correlation was not observed when methylation took place inside gene bodies. Using the literature-based Ingenuity Pathway Analysis, we explored how the differentially methylated genes were related. The analysis showed that increase in cocaine intake by rats in response to DNA methyltransferase inhibitors underlies plasticity mechanisms which mainly concern axonal growth and synaptogenesis as well as spine remodeling. Together with the Akt/PI3K pathway, the Rho-GTPase family was found to be involved in the plasticity underlying the effect of dAZA on the observed behavioral changes.
DOI: 10.1111/gbb.12354
PubMed: 27762100
Affiliations:
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Fonteneau</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Filliol, D" sort="Filliol, D" uniqKey="Filliol D" first="D" last="Filliol">D. Filliol</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Anglard, P" sort="Anglard, P" uniqKey="Anglard P" first="P" last="Anglard">P. Anglard</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Befort, K" sort="Befort, K" uniqKey="Befort K" first="K" last="Befort">K. Befort</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author><author><name sortKey="Romieu, P" sort="Romieu, P" uniqKey="Romieu P" first="P" last="Romieu">P. 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Zwiller</name><affiliation wicri:level="4"><nlm:affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg</wicri:regionArea><placeName><region type="region">Grand Est</region><region type="old region">Alsace (région administrative)</region><settlement type="city">Strasbourg</settlement></placeName><orgName type="university">Université de Strasbourg</orgName></affiliation></author></analytic><series><title level="j">Genes, brain, and behavior</title><idno type="eISSN">1601-183X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals (MeSH)</term><term>Azacitidine (analogs & derivatives)</term><term>Azacitidine (pharmacology)</term><term>Brain (metabolism)</term><term>Cocaine (administration & dosage)</term><term>Cocaine-Related Disorders (enzymology)</term><term>Cocaine-Related Disorders (genetics)</term><term>Cocaine-Related Disorders (metabolism)</term><term>CpG Islands (MeSH)</term><term>Cytidine (analogs & derivatives)</term><term>Cytidine (pharmacology)</term><term>DNA (genetics)</term><term>DNA Methylation (MeSH)</term><term>DNA Modification Methylases (antagonists & inhibitors)</term><term>DNA Modification Methylases (metabolism)</term><term>Decitabine (MeSH)</term><term>Enzyme Inhibitors (pharmacology)</term><term>Epigenesis, Genetic (MeSH)</term><term>Genome (MeSH)</term><term>Male (MeSH)</term><term>Phosphatidylinositol 3-Kinases (metabolism)</term><term>Promoter Regions, Genetic (MeSH)</term><term>Rats (MeSH)</term><term>Rats, Wistar (MeSH)</term><term>Reinforcement, Psychology (MeSH)</term><term>Self Administration (MeSH)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>ADN (génétique)</term><term>Animaux (MeSH)</term><term>Antienzymes (pharmacologie)</term><term>Autoadministration (MeSH)</term><term>Azacitidine (analogues et dérivés)</term><term>Azacitidine (pharmacologie)</term><term>Cocaïne (administration et posologie)</term><term>Cytidine (analogues et dérivés)</term><term>Cytidine (pharmacologie)</term><term>DNA modification methylases (antagonistes et inhibiteurs)</term><term>DNA modification methylases (métabolisme)</term><term>Décitabine (MeSH)</term><term>Encéphale (métabolisme)</term><term>Génome (MeSH)</term><term>Ilots CpG (MeSH)</term><term>Mâle (MeSH)</term><term>Méthylation de l'ADN (MeSH)</term><term>Phosphatidylinositol 3-kinases (métabolisme)</term><term>Rat Wistar (MeSH)</term><term>Rats (MeSH)</term><term>Régions promotrices (génétique) (MeSH)</term><term>Troubles liés à la cocaïne (enzymologie)</term><term>Troubles liés à la cocaïne (génétique)</term><term>Troubles liés à la cocaïne (métabolisme)</term><term>Épigenèse génétique (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Cocaine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Azacitidine</term><term>Cytidine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="antagonists & inhibitors" xml:lang="en"><term>DNA Modification Methylases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>DNA</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>DNA Modification Methylases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Azacitidine</term><term>Cytidine</term><term>Enzyme Inhibitors</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Cocaïne</term></keywords><keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Azacitidine</term><term>Cytidine</term></keywords><keywords scheme="MESH" qualifier="antagonistes et inhibiteurs" xml:lang="fr"><term>DNA modification methylases</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Troubles liés à la cocaïne</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Cocaine-Related Disorders</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Cocaine-Related Disorders</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>ADN</term><term>Troubles liés à la cocaïne</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Cocaine-Related Disorders</term><term>Phosphatidylinositol 3-Kinases</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>DNA modification methylases</term><term>Encéphale</term><term>Phosphatidylinositol 3-kinases</term><term>Troubles liés à la cocaïne</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antienzymes</term><term>Azacitidine</term><term>Cytidine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>CpG Islands</term><term>DNA Methylation</term><term>Decitabine</term><term>Epigenesis, Genetic</term><term>Genome</term><term>Male</term><term>Promoter Regions, Genetic</term><term>Rats</term><term>Rats, Wistar</term><term>Reinforcement, Psychology</term><term>Self Administration</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Autoadministration</term><term>Décitabine</term><term>Génome</term><term>Ilots CpG</term><term>Mâle</term><term>Méthylation de l'ADN</term><term>Rat Wistar</term><term>Rats</term><term>Régions promotrices (génétique)</term><term>Épigenèse génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine (dAZA) and zebularine enhanced the reinforcing properties of cocaine. To obtain some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated with or without dAZA. The study identified nearly 189 000 differentially methylated regions (DMRs), about half of them were located inside gene bodies, while only 9% of DMRs were found in the promoter regions of genes. About 99% of methylation changes occurred outside CpG islands. Gene expression studies confirmed the inverse correlation usually observed between increased methylation and transcriptional activation when methylation occurs in the gene promoter. This inverse correlation was not observed when methylation took place inside gene bodies. Using the literature-based Ingenuity Pathway Analysis, we explored how the differentially methylated genes were related. The analysis showed that increase in cocaine intake by rats in response to DNA methyltransferase inhibitors underlies plasticity mechanisms which mainly concern axonal growth and synaptogenesis as well as spine remodeling. Together with the Akt/PI3K pathway, the Rho-GTPase family was found to be involved in the plasticity underlying the effect of dAZA on the observed behavioral changes.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27762100</PMID><DateCompleted><Year>2017</Year><Month>06</Month><Day>28</Day></DateCompleted><DateRevised><Year>2019</Year><Month>12</Month><Day>10</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1601-183X</ISSN><JournalIssue CitedMedium="Internet"><Volume>16</Volume><Issue>3</Issue><PubDate><Year>2017</Year><Month>03</Month></PubDate></JournalIssue><Title>Genes, brain, and behavior</Title><ISOAbbreviation>Genes Brain Behav</ISOAbbreviation></Journal><ArticleTitle>Inhibition of DNA methyltransferases regulates cocaine self-administration by rats: a genome-wide DNA methylation study.</ArticleTitle><Pagination><MedlinePgn>313-327</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/gbb.12354</ELocationID><Abstract><AbstractText>DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine (dAZA) and zebularine enhanced the reinforcing properties of cocaine. To obtain some insights about the underlying neurobiological mechanisms, a genome-wide methylation analysis was undertaken in the prefrontal cortex of rats self-administering cocaine and treated with or without dAZA. The study identified nearly 189 000 differentially methylated regions (DMRs), about half of them were located inside gene bodies, while only 9% of DMRs were found in the promoter regions of genes. About 99% of methylation changes occurred outside CpG islands. Gene expression studies confirmed the inverse correlation usually observed between increased methylation and transcriptional activation when methylation occurs in the gene promoter. This inverse correlation was not observed when methylation took place inside gene bodies. Using the literature-based Ingenuity Pathway Analysis, we explored how the differentially methylated genes were related. The analysis showed that increase in cocaine intake by rats in response to DNA methyltransferase inhibitors underlies plasticity mechanisms which mainly concern axonal growth and synaptogenesis as well as spine remodeling. Together with the Akt/PI3K pathway, the Rho-GTPase family was found to be involved in the plasticity underlying the effect of dAZA on the observed behavioral changes.</AbstractText><CopyrightInformation>© 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fonteneau</LastName><ForeName>M</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Filliol</LastName><ForeName>D</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anglard</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Befort</LastName><ForeName>K</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Romieu</LastName><ForeName>P</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zwiller</LastName><ForeName>J</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Laboratoire de Neurosciences Cognitives et Adaptatives, UMR 7364, CNRS, Université de Strasbourg, Strasbourg, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>11</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Genes Brain Behav</MedlineTA><NlmUniqueID>101129617</NlmUniqueID><ISSNLinking>1601-183X</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004791">Enzyme Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>5CSZ8459RP</RegistryNumber><NameOfSubstance UI="D003562">Cytidine</NameOfSubstance></Chemical><Chemical><RegistryNumber>776B62CQ27</RegistryNumber><NameOfSubstance UI="D000077209">Decitabine</NameOfSubstance></Chemical><Chemical><RegistryNumber>7A9Y5SX0GY</RegistryNumber><NameOfSubstance UI="C009131">pyrimidin-2-one beta-ribofuranoside</NameOfSubstance></Chemical><Chemical><RegistryNumber>9007-49-2</RegistryNumber><NameOfSubstance UI="D004247">DNA</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.1.1.-</RegistryNumber><NameOfSubstance UI="D015254">DNA Modification Methylases</NameOfSubstance></Chemical><Chemical><RegistryNumber>I5Y540LHVR</RegistryNumber><NameOfSubstance UI="D003042">Cocaine</NameOfSubstance></Chemical><Chemical><RegistryNumber>M801H13NRU</RegistryNumber><NameOfSubstance UI="D001374">Azacitidine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001374" MajorTopicYN="N">Azacitidine</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003042" MajorTopicYN="N">Cocaine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="Y">administration & dosage</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019970" MajorTopicYN="N">Cocaine-Related Disorders</DescriptorName><QualifierName UI="Q000201" MajorTopicYN="N">enzymology</QualifierName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018899" MajorTopicYN="N">CpG Islands</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003562" MajorTopicYN="N">Cytidine</DescriptorName><QualifierName UI="Q000031" MajorTopicYN="N">analogs & derivatives</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004247" MajorTopicYN="N">DNA</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019175" MajorTopicYN="Y">DNA Methylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015254" MajorTopicYN="N">DNA Modification Methylases</DescriptorName><QualifierName UI="Q000037" MajorTopicYN="Y">antagonists & inhibitors</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000077209" MajorTopicYN="N">Decitabine</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004791" MajorTopicYN="N">Enzyme Inhibitors</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D044127" MajorTopicYN="N">Epigenesis, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016678" MajorTopicYN="N">Genome</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019869" MajorTopicYN="N">Phosphatidylinositol 3-Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011401" MajorTopicYN="N">Promoter Regions, Genetic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017208" MajorTopicYN="N">Rats, Wistar</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012054" MajorTopicYN="N">Reinforcement, Psychology</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D012646" MajorTopicYN="N">Self Administration</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y"> DNA methylation</Keyword><Keyword MajorTopicYN="Y"> DNMT inhibitor</Keyword><Keyword MajorTopicYN="Y">5-Aza-2′-deoxycytidine</Keyword><Keyword MajorTopicYN="Y">cocaine self-administration</Keyword><Keyword MajorTopicYN="Y">methylome</Keyword><Keyword MajorTopicYN="Y">prefrontal cortex</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>07</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2016</Year><Month>10</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>10</Month><Day>18</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>6</Month><Day>29</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2016</Year><Month>10</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">27762100</ArticleId><ArticleId IdType="doi">10.1111/gbb.12354</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>France</li></country><region><li>Alsace (région administrative)</li><li>Grand Est</li></region><settlement><li>Strasbourg</li></settlement><orgName><li>Université de Strasbourg</li></orgName></list><tree><country name="France"><region name="Grand Est"><name sortKey="Fonteneau, M" sort="Fonteneau, M" uniqKey="Fonteneau M" first="M" last="Fonteneau">M. Fonteneau</name></region><name sortKey="Anglard, P" sort="Anglard, P" uniqKey="Anglard P" first="P" last="Anglard">P. Anglard</name><name sortKey="Befort, K" sort="Befort, K" uniqKey="Befort K" first="K" last="Befort">K. Befort</name><name sortKey="Filliol, D" sort="Filliol, D" uniqKey="Filliol D" first="D" last="Filliol">D. Filliol</name><name sortKey="Romieu, P" sort="Romieu, P" uniqKey="Romieu P" first="P" last="Romieu">P. Romieu</name><name sortKey="Zwiller, J" sort="Zwiller, J" uniqKey="Zwiller J" first="J" last="Zwiller">J. Zwiller</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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