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1、18Rndfamilygenesaredifferentiallyregulatedby3,4-methylenedioxymethamphetamineandcocaineacutetreatmentinmicebrainCynthiaMarie-Claire,JulieSalzmann,AlexandreDavid,CindieCourtin,CorinneCanestrelli,FlorenceNoble*CNRS,UMR7157 ;INSERM,U705 ;UniversiteParisDescartes,N
2、europsychopharmacologiedesaddictions,Paris,F-75006FranceNumberofpages :18Numberoffiguresandtables:4*correspondingauthorTel:33-1-53-73-95-61Fax:33-1-53-73-97-19florence.noble@univ-paris5.fr181-ABSTRACTDrugsofabuseinducealterationsincytoskeletalandcytoskeletonass
3、ociatedgenesinseveralbrainareas.WehavepreviouslyshownthatacuteMDMAregulatesthemRNAlevelofRnd3,aRhoGTPaseinvolvedinactincytoskeletonregulation,inmicestriatum.Inthisstudyweinvestigatedtheeffectsofsingleadministrationofcocaine,anotherpsychostimulantwithaslightlydi
4、fferentmechanismofaction,onthemRNAlevelsofthethreemembersoftheRndgenesfamily(Rnd1,Rnd2andRnd3).MiceweretreatedwitheitherMDMA(9mg/kg)andcocaine(20mg/jg)andbrainsamples(i.e.hippocampus,striatumandprefrontalcortex)wereprocessedforquantitativereal-timePCRassayone,t
5、wo,fourandsixhoursaftertheinjections.TheexpressionlevelofRnd2wasdifferentiallyaffecteddependingonthedrug,brainareaandtimepointafterinjection.InterestinglythetwodrugsupregulateRnd3geneexpressioninthethreestructurestestedwithsomedifferencesinthetiming.Theeffectso
6、fMDMAonRnd3appearearlierinthehippocampusascomparedtococaine,whileitistheoppositeintheprefrontalcortex.HoweverinthedorsalstriatumthetwodrugsinduceanearlyandsignificantupregulationofRnd3expressionthatislonger-lastinginthecaseofMDMA.Inthecaseofcocainecontrarilytow
7、hatwasobservedwithMDMAthismodulationcouldnotbeblockedwiththeERKactivationinhibitorSL327suggestingthatthetwodrugsleadtothesameeffectonRnd3bytwodistinctpathways.Section1:CellularandMolecularBiologyofNervousSystemsKeywords :cocaine,Rnd3,MDMA,geneexpression,acute18
8、Abbreviations:PCR,polymerasechainreaction ;DMSO,dimethylsulfoxide;MDMA:3,4-methylenedioxymethamphetamine182-INTRODUCTIONAlargebodyofliteratureindicatesthattheexpressionandfu
