Rnd family genes are differentially regulated by 3,4-methylenedioxymethamphetamine and cocaine acute treatment in mice brain.
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) or cocaine (20 mg/jg) and brain samples (i.e. hippocampus, striatum and prefrontal cortex) were processed for quantitative real-time PCR assay 1, 2, 4 and 6 h 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 up-regulate 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 up-regulation 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 by two distinct pathways.
Marie-Claire
Cynthia
C
CNRS, UMR7157, INSERM, U705, Universite Paris Descartes, Neuropsychopharmacologie des addictions, Paris, F-75006 France.
Salzmann
Julie
J
David
Alexandre
A
Courtin
Cindie
C
Canestrelli
Corinne
C
Noble
Florence
F
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics*
D018759:Adrenergic Uptake Inhibitors; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; C475019:Rnd2 protein, mouse; C513341:Rnd3 protein, mouse; D020741:rho GTP-Binding Proteins; D003042:Cocaine; D018817:N-Methyl-3,4-methylenedioxyamphetamine