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3,4-Methylenedioxymethamphetamine Induces Gene Expression Changes in Rats Related to Serotonergic and Dopaminergic Systems, But Not to Neurotoxicity

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Abstract

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is an amphetamine derivative widely abused by young adults. Although many studies have reported that relatively high doses of MDMA deplete serotonin (5-HT) content and decrease the availability of serotonin transporters (5-HTT), limited evidence is available as to the adaptive mechanisms taking place in gene expression levels in the brain following a dosing regimen of MDMA comparable to human consumption. In order to further clarify this issue, we used quantitative PCR to study the long-term changes induced by acute administration of MDMA (5 mg/kg × 3) in the expression of genes related to serotonergic and dopaminergic systems, as well as those related to cellular toxicity in the cortex, hippocampus, striatum, and brain stem of rats. Seven days after MDMA administration, we found a significantly lower expression of the 5-HTT (Slc6a4) and the vesicular monoamine transporter (Slc18a2) genes in the brain stem area. In the hippocampus, monoamine oxidase B (Maob) and tryptophan hydroxylase 2 (Tph2) gene expressions were increased. In the striatum, tyrosine hydroxylase (Th) expression was decreased, and a lower expression of α-synuclein (Snca) was observed in the cortex. In contrast, no significant changes were observed in the genes considered to be biomarkers of toxicity including the glial fibrillary acidic protein (Gfap) and the heat-shock 70 kD protein 1A (Hspa1a) in any of the structures assayed. These results suggest that MDMA promotes adaptive changes in genes related to serotonergic and dopaminergic functionality, but not in genes related to neurotoxicity.

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Acknowledgments

This work was supported by grants from DIUE de la Generalitat de Catalunya (2009 SGR 718) and ISCIII-Red de Trastornos Adictivos (RTA: RD12/0028/0009).

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Authors and Affiliations

  1. Human Pharmacology and Clinical Neurosciences Research Group, Neurosciences Research Program, IMIM-Hospital del Mar Medical Research Institute, Parc de Recerca Biomèdica de Barcelona, Doctor Aiguader, 88, 08003, Barcelona, Spain

    Elisabet Cuyas, Patricia Robledo, Nieves Pizarro, Magí Farré & Rafael de la Torre

  2. Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain

    Patricia Robledo & Rafael de la Torre

  3. Department of Pharmacology, University of Navarra, Pamplona, Spain

    Elena Puerta & Norberto Aguirre

  4. CIBER de Fisiopatología de la Obesidad y Nutrición (CB06/03), CIBEROBN, Santiago de Compostela, Spain

    Rafael de la Torre

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  1. Elisabet Cuyas
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  2. Patricia Robledo
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  3. Nieves Pizarro
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  4. Magí Farré
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Correspondence to Rafael de la Torre.

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Cuyas, E., Robledo, P., Pizarro, N. et al. 3,4-Methylenedioxymethamphetamine Induces Gene Expression Changes in Rats Related to Serotonergic and Dopaminergic Systems, But Not to Neurotoxicity. Neurotox Res 25, 161–169 (2014). https://doi.org/10.1007/s12640-013-9416-1

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