Modulation of the Rnd family genes by acute - HAL - INSERM急性---HAL--- INSERM的RND家族基因的调节.docVIP

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Modulation of the Rnd family genes by acute - HAL - INSERM急性---HAL--- INSERM的RND家族基因的调节.doc

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Modulation of the Rnd family genes by acute - HAL - INSERM急性---HAL--- INSERM的RND家族基因的调节.doc

Rnd family genes are differentially regulated by 3,4-methylenedioxymethamphetamine and cocaine acute treatment in mice brain Cynthia Marie-Claire, Julie Salzmann, Alexandre David, Cindie Courtin, Corinne Canestrelli, Florence Noble* CNRS, UMR7157?; INSERM, U705?; Universite Paris Descartes, Neuropsychopharmacologie des addictions, Paris, F-75006 France Number of pages?: 18 Number of figures and tables: 4 * corresponding author Tel : 33-1-53-73-95-61 Fax : 33-1-53-73-97-19 florence.noble@univ-paris5.fr 1- ABSTRACT Drugs of abuse induce alterations in cytoskeletal and cytoskeleton associated genes in several brain areas. We have previously shown that acute MDMA regulates the mRNA level of Rnd3, a Rho GTPase involved in actin cytoskeleton regulation, in mice striatum. In this study we investigated the effects of single administration of cocaine, another psychostimulant with a slightly different mechanism of action, on the mRNA levels of the three members of the Rnd genes family (Rnd1, Rnd2 and Rnd3). Mice were treated with either MDMA (9 mg/kg) and cocaine (20 mg/jg) and brain samples (i.e. hippocampus, striatum and prefrontal cortex) were processed for quantitative real-time PCR assay one, two, four and six hours after the injections. The expression level of Rnd2 was differentially affected depending on the drug, brain area and time point after injection. Interestingly the two drugs upregulate Rnd3 gene expression in the three structures tested with some differences in the timing. The effects of MDMA on Rnd3 appear earlier in the hippocampus as compared to cocaine, while it is the opposite in the prefrontal cortex. However in the dorsal striatum the two drugs induce an early and significant upregulation of Rnd3 expression that is longer-lasting in the case of MDMA. In the case of cocaine contrarily to what was observed with MDMA this modulation could not be blocked with the ERK activation inhibitor SL327 suggesting that the two drugs lead to the same effect on Rnd3