title: Active and passive MDMA ('ecstasy') intake induces differential transcriptional changes in the mouse brain.
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.
authors.affiliation: Departament de Genètica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Fernàndez-Castillo
authors.forename: M J
authors.initials: MJ
authors.lastname: Orejarena
authors.forename: M
authors.initials: M
authors.lastname: Ribasés
authors.forename: E
authors.initials: E
authors.lastname: Blanco
authors.forename: M
authors.initials: M
authors.lastname: Casas
authors.forename: P
authors.initials: P
authors.lastname: Robledo
authors.forename: R
authors.initials: R
authors.lastname: Maldonado
authors.forename: B
authors.initials: B
authors.lastname: Cormand
mesh_terms: D000222:Adaptation, Physiological; D000367:Age Factors; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003216:Conditioning, Operant; D058999:Drug-Seeking Behavior / Q000502:physiology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006213:Hallucinogens / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D012201:Reward; D012646:Self Administration; D014018:Tissue Distribution; D059467:Transcriptome / Q000187:drug effects
chemical_list: D006213:Hallucinogens; D009419:Nerve Tissue Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine