Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice 英文参考文献.docVIP

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Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice 英文参考文献.doc

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Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice 英文参考文献

RoleofSerotoninvia5-HT2BReceptorsintheReinforcing EffectsofMDMAinMice Ste′phaneDoly1,2,JesusBertran-Gonzalez1,2,JacquesCallebert3,4,AlexandraBruneau1,2,SophieMarie Banas1,2,ArnauldBelmer1,2,KatiaBoutourlinsky1,2,DenisHerve′1,2,Jean-MarieLaunay3,4 ,Luc Maroteaux1,2 * 1INSERM U839, Paris, France, 2Universite′ Pierre et Marie Curie, Paris 6, Institut du Fer a` Moulin, UMR-S0839, Paris, France, 3AP-HP, Ho?pital Lariboisie`re, Service de Biochimie,Paris,France,4INSERMU942,Paris,France Abstract The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporterstoproduceeffluxofdopamineandserotonin,respectively,inregionsofthebrainthathavebeenimplicatedin reward. However, the role of serotonin/dopamine interactions in the behavioral effects of MDMA remains unclear. We previouslyshowedthatMDMA-inducedlocomotion,serotoninanddopaminereleaseare5-HT2Breceptor-dependent.The aimofthepresentstudywastodeterminethecontributionofserotoninand5-HT2Breceptorstothereinforcingproperties of MDMA. We show here that 5-HT2B2/2 mice do not exhibit behavioral sensitization or conditioned place preference following MDMA (10mg/kg) injections. In addition, MDMA-induced reinstatement of conditioned place preference after extinctionandlocomotorsensitizationdevelopmentareeachabolishedbya5-HT2Breceptorantagonist(RS127445)inwild type mice. Accordingly, MDMA-induced dopamine D1 receptor-dependent phosphorylation of extracellular regulated kinaseinnucleusaccumbensisabolishedinmicelackingfunctional5-HT2Breceptors.Nevertheless,highdoses(30mg/kg) of MDMAinduce dopamine-dependent but serotonin and5-HT2B receptor-independent behavioraleffects. Theseresults underpintheimportanceof5-HT2BreceptorsinthereinforcingpropertiesofMDMAandillustratetheimportanceofdose- dependenteffectsofMDMAonserotonin/dopamineinteractions. Citation:DolyS,Bertran-GonzalezJ,CallebertJ,BruneauA,BanasSM,etal.(2009)RoleofSerotoninvia5-HT2BReceptorsintheReinforcingEffectsofMDMAin Mice.PL