RETRACTED ARTICLE: Gene expressionanalysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effectsin the frontal cortex 3 weeks after single-dose MDMA administration in Dark Agoutirats

BMC Genomics

Research Article

Viola Tamasi¹  Eszter Kirilly²  Laszlo Tothfalusi²  Romeo D Ando²  Csaba Adori²  Gyorgy Bagdy³  Peter Petschner³ 

[1] Department of Genetics, Cell- and Immunobiology, Semmelweis University, Nagyvarad ter 4., H-1089, Budapest, Hungary;Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4., H-1089, Budapest, Hungary;Department of Pharmacodynamics, Semmelweis University, Nagyvarad ter 4., H-1089, Budapest, Hungary;MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Budapest, Hungary;

关键词: MDMA;    Ecstasy;    Endocannabinoid;    CB1;    Addiction;    Cognition;    Memory;    Rat;    Gene expression;    Microarray;   

DOI  :  10.1186/1471-2164-14-930

 received in 2013-07-19, accepted in 2013-12-23,  发布年份 2013

来源: Springer

【 摘 要 】

Background3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely usedrecreational drug known to impair cognitive functions on the long-run. Bothhippocampal and frontal cortical regions have well established roles in behavior,memory formation and other cognitive tasks and damage of these regions isassociated with altered behavior and cognitive functions, impairments frequentlydescribed in heavy MDMA users. The aim of this study was to examine thehippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with geneexpression arrays (Illumina RatRef bead arrays) looking for possible mechanismsand new candidates contributing to the effects of a single dose of MDMA (15 mg/kg)3 weeks earlier.ResultsThe number of differentially expressed genes in the hippocampus, frontalcortex and the dorsal raphe were 481, 155, and 15, respectively. Gene setenrichment analysis of the microarray data revealed reduced expression of 'memory’and 'cognition’, 'dendrite development’ and 'regulation of synaptic plasticity’gene sets in the hippocampus, parallel to the upregulation of the CB1 cannabinoid-and Epha4, Epha5, Epha6 ephrin receptors.Downregulated gene sets in the frontal cortex were related to protein synthesis,chromatin organization, transmembrane transport processes, while 'dendritedevelopment’, 'regulation of synaptic plasticity’ and 'positive regulation ofsynapse assembly’ gene sets were upregulated. Changes in the dorsal raphe regionwere mild and in most cases not significant.ConclusionThe present data raise the possibility of new synapse formation/synapticreorganization in the frontal cortex three weeks after a single neurotoxic dose ofMDMA. In contrast, a prolonged depression of new neurite formation in thehippocampus is suggested by the data, which underlines the particularvulnerability of this brain region after the drug treatment. Finally, our resultsalso suggest the substantial contribution of CB1 receptor and endocannabinoidmediated pathways in the hippocampal impairments. Taken together the present studyprovides evidence for the participation of new molecular candidates in thelong-term effects of MDMA.

【 授权许可】

Unknown   
© Petschner et al.; licensee BioMed CentralLtd. 2013. This article is published under license to BioMed Central Ltd. This isan open access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.