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Analysis of transcriptional responses in the mouse dorsal striatum following acute 3,4-methylenedioxymethamphetamine (ecstasy): identification of extracellular signal-regulated kinase-controlled genes.

Julie Salzmann, C Canestrelli, Florence Noble, Cynthia Marie‐claire

Neuroscience 2006 DOI: 10.1016/j.neuroscience.2005.09.019 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Experimental study Peer reviewed
Population Mice
Intervention SL327
Topics MDMA
Key findings MDMA activates ERK in the dorsal striatum and alters expression of 27 genes, with 59% of these changes dependent on ERK activation, implicating these molecular changes in MDMA's behavioral effects.

Abstract

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.

Comparable studies

Other preclinical and animal studies on MDMA, most cited first.

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