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

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  • dc.contributor.author Fernández Castillo, Noeliaca
  • dc.contributor.author Orejarena Serrano, María-Juliana, 1980-ca
  • dc.contributor.author Ribasés, Martaca
  • dc.contributor.author Casas, Miguelca
  • dc.contributor.author Robledo, Patricia, 1958-ca
  • dc.contributor.author Maldonado, Rafael, 1961-ca
  • dc.contributor.author Cormand, Bruca
  • dc.date.accessioned 2015-03-31T10:18:03Z
  • dc.date.available 2015-03-31T10:18:03Z
  • dc.date.issued 2012ca
  • 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/pdfca
  • 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.xca
  • dc.identifier.doi http://dx.doi.org/10.1111/j.1601-183X.2011.00735.x
  • dc.identifier.issn 1601-1848ca
  • dc.identifier.uri http://hdl.handle.net/10230/23315
  • dc.language.iso engca
  • dc.publisher Wiley-Blackwellca
  • dc.relation.ispartof Genes, Brain and Behavior. 2012;11(1):38-51
  • 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 © Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.comca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • 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 brainca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/acceptedVersionca

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