Analysis of transcriptional responses in the mouse dorsal striatum following acute 3,4-methylenedioxymethamphetamine (ecstasy): identification of extracellular signal-regulated kinase-controlled genes.
3,4-Methylenedioxymethamphetamine (ecstasy), a widely used recreational drug with psychoactive properties, induces both serotonin and dopamine release in the brain. However, little is known about its intracellular effects. We previously showed that 3,4-methylenedioxymethamphetamine rewarding effects in mice were dependent upon extracellular signal-regulated kinase activation and that dorsal striatum was a critical region for mediating extracellular signal-regulated kinase-dependent Egr1 3,4-methylenedioxymethamphetamine-induced transcription. Here, we extend these findings by showing that 3,4-methylenedioxymethamphetamine is indeed able to activate extracellular signal-regulated kinase within this structure. To identify genes regulated by acute 3,4-methylenedioxymethamphetamine in the mice dorsal striatum, and selectively controlled by this kinase, we performed microarray experiments by using a selective inhibitor of extracellular signal-regulated kinase activation, SL327. Of the approximately 24,000 genes from the microarray, 27 showed altered expression after exposure to 3,4-methylenedioxymethamphetamine, and among these, 59% were partially or totally inhibited by SL327 pretreatment. Our results showed that the genes regulated by 3,4-methylenedioxymethamphetamine encode proteins that belong to transcription factors family, signaling pathways (phosphatases, cytoskeleton regulation), and synaptic functions. These early changes, and especially those controlled by extracellular signal-regulated kinase activation might play significant roles in the expression of many of the behaviors that occur following 3,4-methylenedioxymethamphetamine taking.
Salzmann
J
J
Université Paris Descartes, INSERM U705, CNRS UMR 7157, Laboratoire de Neuropsychopharmacologie des Addictions, 4 Avenue de l'Observatoire, 75270 Paris Cedex 06, France.
Canestrelli
C
C
Noble
F
F
Marie-Claire
C
C
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006213:Hallucinogens / Q000494:pharmacology; D008297:Male; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D017072:Neostriatum / Q000187:drug effects* / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D003598:Cytoskeletal Proteins; D006213:Hallucinogens; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D018817:N-Methyl-3,4-methylenedioxyamphetamine