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Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain

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dc.contributor.author Fernández Castillo, Noelia
dc.contributor.author Orejarena Serrano, María-Juliana, 1980-
dc.contributor.author Ribasés, Marta
dc.contributor.author Casas, Miguel
dc.contributor.author Robledo, Patricia, 1958-
dc.contributor.author Maldonado, Rafael, 1961-
dc.contributor.author Cormand, Bru
dc.date.accessioned 2015-03-31T10:18:03Z
dc.date.available 2015-03-31T10:18:03Z
dc.date.issued 2012
dc.identifier.citation Fernàndez-Castillo N, Orejarena MJ, Ribasés M et al. Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain. Genes, Brain and Behavior. 2012;11(1):38-51. DOI: 10.1111/j.1601-183X.2011.00735.x
dc.identifier.issn 1601-1848
dc.identifier.uri http://hdl.handle.net/10230/23315
dc.description.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.
dc.description.sponsorship This work was supported by the Spanish ‘Ministerio de Ciencia e Innovación (MICINN)’(SAF2007-64062), ‘Instituto de Salud Carlos III’ (RD06/001/001 and PI070709), the Catalan Government (SGR2009-00131 and SGR2009-00971), the ICREA Foundation (ICREA Academia-2008), ‘Plan Nacional Sobre Drogas’ (PNSD#2009/022 and PNSD#2009/026), Fundació ‘La Marató/nde TV3’ (2007) and the DG Research of the European Commission (GENADDICT, LSHM-CT-2004-05166; and PHECOMP, LSHM-CT-2007-037669). Partial support from FEDER funds is/nalso acknowledged. MR is a recipient of a Miguel de Servet contract from ‘Instituto de Salud Carlos III-MICINN’ (Spain) and NF-C was supported by a fellowship from the Biomedical Network/nResearch Centre on Rare Diseases (CIBERER)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley-Blackwell
dc.relation.ispartof Genes, Brain and Behavior. 2012;11(1):38-51
dc.rights © Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
dc.subject.other Drogues -- Efectes secundaris
dc.subject.other Cervell
dc.subject.other Expressió gènica
dc.subject.other Al·lucinògens -- Farmacologia
dc.title Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1111/j.1601-183X.2011.00735.x
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/05166
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP6/037669
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/acceptedVersion

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