RETRACTED ARTICLE: Gene expressionanalysis indicates CB1 receptor upregulation in the hippocampus and neurotoxic effectsin the frontal cortex 3 weeks after single-dose MDMA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

[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.

[发布日期] 2013-12-30

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