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Characteristics of dual specificity phosphatases mRNA regulation by 3,4-methylenedioxymethamphetamine acute treatment in mice striatum.

Cynthia Marie‐claire, Nadia Benturquia, Ann Lundqvist, Cindie Courtin, Florence Noble

Brain Research November 6, 2008 DOI: 10.1016/j.brainres.2008.08.050 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Basic science study in mice Peer reviewed
Population Mice striatum
Intervention MDMA
Topics MDMA
Key points The increase in Dusp14 mRNA after acute MDMA treatment depends on ERK activation and persists longer than increases in Dusp1 and Dusp5. All three Dusp mRNAs are partially dependent on D1 receptor activation but independent of D2 receptor activation. The authors suggest at least two separate signalling cascades up-regulate these phosphatases, with Dusp14 serving as a direct negative-feedback mechanism of MDMA-induced ERK signalling.

Abstract

3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug that has rewarding properties in rodents but little is known about its effects at the cellular and molecular levels. We have previously shown that the ERK pathway is important for the regulation in gene expression observed in mice striatum after acute treatment with MDMA. Interestingly, three dual specificity phosphatases were found among the genes modulated by MDMA acute treatment. In this study we investigated the signalling pathways leading to the up-regulation of these three mRNAs and the kinetics of their regulation. We found that the increase in Dusp14 mRNA depends on the activation of ERK and lasts longer than those of Dusp1 and Dusp5. The modulation of the three studied Dusps depends partially on the activation of D1 receptors but is independent of the activation of D2 receptors. These results suggest that at least two separate signalling cascades lead to the up-regulation of MAPK phosphatase mRNAs. The increase of Dusp1 and Dusp5 mRNAs is not controlled by ERK activation while that of Dusp14 is a direct negative-feedback mechanism of MDMA-induced ERK signalling. Both mechanisms converge to increase the expression levels of phosphatases able to inactivate ERK.

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