Active and passive MDMA (‘ecstasy’) intake induces differential transcriptional changes in the mouse brain
3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a recreational drug widely used by adolescents and young adults. Although its rewarding effects are well established, there is controversy on its addictive potential. We aimed to compare the consequences of active and passive MDMA administration...
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| creator | Fernàndez‐Castillo, N. Orejarena, M. J. Ribasés, M. Blanco, E. Casas, M. Robledo, P. Maldonado, R. Cormand, B. |
| description | 3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a recreational drug widely used by adolescents and young adults. Although its rewarding effects are well established, there is controversy on its addictive potential. We aimed to compare the consequences of active and passive MDMA administration on gene expression in the mouse brain since all previous studies were based on passive MDMA administration. We used a yoked‐control operant intravenous self‐administration paradigm combined with microarray technology. Transcriptomic profiles of ventral striatum, frontal cortex, dorsal raphe nucleus and hippocampus were analysed in mice divided in contingent MDMA, yoked MDMA and yoked saline groups, and several changes were validated by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The comparison of contingent MDMA and yoked MDMA vs. yoked saline mice allowed the identification of differential expression in several genes, most of them with immunological and inflammatory functions, but others being involved in neuroadaptation. In the comparison of contingent MDMA vs. yoked MDMA administration, hippocampus and the dorsal raphe nucleus showed statistically significant changes. The altered expression of several genes involved in neuroadaptative changes and synapse function, which may be related to learning self‐administration behaviour, could be validated in these two brain structures. In conclusion, our study shows a strong effect of MDMA administration on the expression of immunological and inflammatory genes in all the four brain regions studied. In addition, experiments on MDMA self‐administration suggest that the dorsal raphe nucleus and hippocampus may be involved in active MDMA‐seeking behaviour, and show specific alterations on gene expression that support the addictive potential of this drug. |
| doi_str_mv | 10.1111/j.1601-183X.2011.00735.x |
| format | Article |
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J. ; Ribasés, M. ; Blanco, E. ; Casas, M. ; Robledo, P. ; Maldonado, R. ; Cormand, B.</creator><creatorcontrib>Fernàndez‐Castillo, N. ; Orejarena, M. J. ; Ribasés, M. ; Blanco, E. ; Casas, M. ; Robledo, P. ; Maldonado, R. ; Cormand, B.</creatorcontrib><description>3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a recreational drug widely used by adolescents and young adults. Although its rewarding effects are well established, there is controversy on its addictive potential. We aimed to compare the consequences of active and passive MDMA administration on gene expression in the mouse brain since all previous studies were based on passive MDMA administration. We used a yoked‐control operant intravenous self‐administration paradigm combined with microarray technology. Transcriptomic profiles of ventral striatum, frontal cortex, dorsal raphe nucleus and hippocampus were analysed in mice divided in contingent MDMA, yoked MDMA and yoked saline groups, and several changes were validated by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The comparison of contingent MDMA and yoked MDMA vs. yoked saline mice allowed the identification of differential expression in several genes, most of them with immunological and inflammatory functions, but others being involved in neuroadaptation. In the comparison of contingent MDMA vs. yoked MDMA administration, hippocampus and the dorsal raphe nucleus showed statistically significant changes. The altered expression of several genes involved in neuroadaptative changes and synapse function, which may be related to learning self‐administration behaviour, could be validated in these two brain structures. In conclusion, our study shows a strong effect of MDMA administration on the expression of immunological and inflammatory genes in all the four brain regions studied. In addition, experiments on MDMA self‐administration suggest that the dorsal raphe nucleus and hippocampus may be involved in active MDMA‐seeking behaviour, and show specific alterations on gene expression that support the addictive potential of this drug.</description><identifier>ISSN: 1601-1848</identifier><identifier>EISSN: 1601-183X</identifier><identifier>DOI: 10.1111/j.1601-183X.2011.00735.x</identifier><identifier>PMID: 21951708</identifier><identifier>CODEN: GBBEAO</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adaptation, Physiological ; Addiction ; Adolescence ; Age Factors ; Al·lucinògens ; Animals ; Basal Ganglia - drug effects ; Basal Ganglia - metabolism ; Brain ; Brain - drug effects ; Brain - metabolism ; Cervell ; Conditioning, Operant ; Cortex (frontal) ; DNA microarrays ; dorsal raphe nucleus ; Drogues ; Drug abuse ; Drug-Seeking Behavior - physiology ; Ecstasy ; Efectes secundaris ; Expressió gènica ; Farmacologia ; Frontal Lobe - drug effects ; Frontal Lobe - metabolism ; Gene expression ; Gene Expression Regulation - drug effects ; Hallucinogens - pharmacology ; Hippocampus ; Hippocampus - drug effects ; Hippocampus - metabolism ; Humans ; Inflammation ; Intravenous administration ; Learning ; Male ; MDMA ; Medical research ; Mice ; Mice, Inbred C57BL ; Microarray Analysis ; mouse brain ; N-Methyl-3,4-methylenedioxyamphetamine - pharmacology ; Neostriatum ; Nerve Tissue Proteins - drug effects ; Nerve Tissue Proteins - metabolism ; Operant conditioning ; Polymerase chain reaction ; Raphe Nuclei - drug effects ; Raphe Nuclei - metabolism ; Reinforcement ; Reverse transcription ; Reward ; Self Administration ; Statistical analysis ; Synapses ; Tissue Distribution ; Transcription ; Transcriptome - drug effects ; transcriptomics</subject><ispartof>Genes, brain and behavior, 2012-02, Vol.11 (1), p.38-51</ispartof><rights>2011 The Authors. 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J.</creatorcontrib><creatorcontrib>Ribasés, M.</creatorcontrib><creatorcontrib>Blanco, E.</creatorcontrib><creatorcontrib>Casas, M.</creatorcontrib><creatorcontrib>Robledo, P.</creatorcontrib><creatorcontrib>Maldonado, R.</creatorcontrib><creatorcontrib>Cormand, B.</creatorcontrib><title>Active and passive MDMA (‘ecstasy’) intake induces differential transcriptional changes in the mouse brain</title><title>Genes, brain and behavior</title><addtitle>Genes Brain Behav</addtitle><description>3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a recreational drug widely used by adolescents and young adults. Although its rewarding effects are well established, there is controversy on its addictive potential. We aimed to compare the consequences of active and passive MDMA administration on gene expression in the mouse brain since all previous studies were based on passive MDMA administration. We used a yoked‐control operant intravenous self‐administration paradigm combined with microarray technology. Transcriptomic profiles of ventral striatum, frontal cortex, dorsal raphe nucleus and hippocampus were analysed in mice divided in contingent MDMA, yoked MDMA and yoked saline groups, and several changes were validated by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The comparison of contingent MDMA and yoked MDMA vs. yoked saline mice allowed the identification of differential expression in several genes, most of them with immunological and inflammatory functions, but others being involved in neuroadaptation. In the comparison of contingent MDMA vs. yoked MDMA administration, hippocampus and the dorsal raphe nucleus showed statistically significant changes. The altered expression of several genes involved in neuroadaptative changes and synapse function, which may be related to learning self‐administration behaviour, could be validated in these two brain structures. In conclusion, our study shows a strong effect of MDMA administration on the expression of immunological and inflammatory genes in all the four brain regions studied. 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J.</au><au>Ribasés, M.</au><au>Blanco, E.</au><au>Casas, M.</au><au>Robledo, P.</au><au>Maldonado, R.</au><au>Cormand, B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Active and passive MDMA (‘ecstasy’) intake induces differential transcriptional changes in the mouse brain</atitle><jtitle>Genes, brain and behavior</jtitle><addtitle>Genes Brain Behav</addtitle><date>2012-02</date><risdate>2012</risdate><volume>11</volume><issue>1</issue><spage>38</spage><epage>51</epage><pages>38-51</pages><issn>1601-1848</issn><eissn>1601-183X</eissn><coden>GBBEAO</coden><abstract>3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) is a recreational drug widely used by adolescents and young adults. Although its rewarding effects are well established, there is controversy on its addictive potential. We aimed to compare the consequences of active and passive MDMA administration on gene expression in the mouse brain since all previous studies were based on passive MDMA administration. We used a yoked‐control operant intravenous self‐administration paradigm combined with microarray technology. Transcriptomic profiles of ventral striatum, frontal cortex, dorsal raphe nucleus and hippocampus were analysed in mice divided in contingent MDMA, yoked MDMA and yoked saline groups, and several changes were validated by quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The comparison of contingent MDMA and yoked MDMA vs. yoked saline mice allowed the identification of differential expression in several genes, most of them with immunological and inflammatory functions, but others being involved in neuroadaptation. In the comparison of contingent MDMA vs. yoked MDMA administration, hippocampus and the dorsal raphe nucleus showed statistically significant changes. The altered expression of several genes involved in neuroadaptative changes and synapse function, which may be related to learning self‐administration behaviour, could be validated in these two brain structures. In conclusion, our study shows a strong effect of MDMA administration on the expression of immunological and inflammatory genes in all the four brain regions studied. In addition, experiments on MDMA self‐administration suggest that the dorsal raphe nucleus and hippocampus may be involved in active MDMA‐seeking behaviour, and show specific alterations on gene expression that support the addictive potential of this drug.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21951708</pmid><doi>10.1111/j.1601-183X.2011.00735.x</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptation, Physiological Addiction Adolescence Age Factors Al·lucinògens Animals Basal Ganglia - drug effects Basal Ganglia - metabolism Brain Brain - drug effects Brain - metabolism Cervell Conditioning, Operant Cortex (frontal) DNA microarrays dorsal raphe nucleus Drogues Drug abuse Drug-Seeking Behavior - physiology Ecstasy Efectes secundaris Expressió gènica Farmacologia Frontal Lobe - drug effects Frontal Lobe - metabolism Gene expression Gene Expression Regulation - drug effects Hallucinogens - pharmacology Hippocampus Hippocampus - drug effects Hippocampus - metabolism Humans Inflammation Intravenous administration Learning Male MDMA Medical research Mice Mice, Inbred C57BL Microarray Analysis mouse brain N-Methyl-3,4-methylenedioxyamphetamine - pharmacology Neostriatum Nerve Tissue Proteins - drug effects Nerve Tissue Proteins - metabolism Operant conditioning Polymerase chain reaction Raphe Nuclei - drug effects Raphe Nuclei - metabolism Reinforcement Reverse transcription Reward Self Administration Statistical analysis Synapses Tissue Distribution Transcription Transcriptome - drug effects transcriptomics |
| title | Active and passive MDMA (‘ecstasy’) intake induces differential transcriptional changes in the mouse brain |
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