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 M...

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Detalhes bibliográficos
Autores: Fernández Castillo, Noelia, Orejarena Serrano, María-Juliana, 1980-, Ribasés, Marta, Casas, Miguel, Robledo, Patricia, 1958-, Maldonado, Rafael, 1961-, Cormand, Bru
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2012
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/23315
Acesso em linha:http://hdl.handle.net/10230/23315
http://dx.doi.org/10.1111/j.1601-183X.2011.00735.x
Access Level:acceso abierto
Palavra-chave:Drogues -- Efectes secundaris
Cervell
Expressió gènica
Al·lucinògens -- Farmacologia
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spelling Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brainFernández Castillo, NoeliaOrejarena Serrano, María-Juliana, 1980-Ribasés, MartaCasas, MiguelRobledo, Patricia, 1958-Maldonado, Rafael, 1961-Cormand, BruDrogues -- Efectes secundarisCervellExpressió gènicaAl·lucinògens -- Farmacologia3,4-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.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)Wiley-Blackwell201520152012info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23315http://dx.doi.org/10.1111/j.1601-183X.2011.00735.xreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésGenes, Brain and Behavior. 2012;11(1):38-51info:eu-repo/grantAgreement/EC/FP6/05166info:eu-repo/grantAgreement/EC/FP6/037669info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062© Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.cominfo:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/233152026-06-12T07:21:37Z
dc.title.none.fl_str_mv Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
title Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
spellingShingle Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
Fernández Castillo, Noelia
Drogues -- Efectes secundaris
Cervell
Expressió gènica
Al·lucinògens -- Farmacologia
title_short Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
title_full Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
title_fullStr Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
title_full_unstemmed Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
title_sort Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain
dc.creator.none.fl_str_mv Fernández Castillo, Noelia
Orejarena Serrano, María-Juliana, 1980-
Ribasés, Marta
Casas, Miguel
Robledo, Patricia, 1958-
Maldonado, Rafael, 1961-
Cormand, Bru
author Fernández Castillo, Noelia
author_facet Fernández Castillo, Noelia
Orejarena Serrano, María-Juliana, 1980-
Ribasés, Marta
Casas, Miguel
Robledo, Patricia, 1958-
Maldonado, Rafael, 1961-
Cormand, Bru
author_role author
author2 Orejarena Serrano, María-Juliana, 1980-
Ribasés, Marta
Casas, Miguel
Robledo, Patricia, 1958-
Maldonado, Rafael, 1961-
Cormand, Bru
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Drogues -- Efectes secundaris
Cervell
Expressió gènica
Al·lucinògens -- Farmacologia
topic Drogues -- Efectes secundaris
Cervell
Expressió gènica
Al·lucinògens -- Farmacologia
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.
publishDate 2012
dc.date.none.fl_str_mv 2012
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/23315
http://dx.doi.org/10.1111/j.1601-183X.2011.00735.x
url http://hdl.handle.net/10230/23315
http://dx.doi.org/10.1111/j.1601-183X.2011.00735.x
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genes, Brain and Behavior. 2012;11(1):38-51
info:eu-repo/grantAgreement/EC/FP6/05166
info:eu-repo/grantAgreement/EC/FP6/037669
info:eu-repo/grantAgreement/ES/2PN/SAF2007-64062
dc.rights.none.fl_str_mv © Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
info:eu-repo/semantics/openAccess
rights_invalid_str_mv © Wiley-Blackwell. The definitive version is available at www3.interscience.wiley.com
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-Blackwell
publisher.none.fl_str_mv Wiley-Blackwell
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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