GPR3 Receptor, a Novel Actor in the Emotional-Like Responses 英文参考文献.docVIP

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GPR3 Receptor, a Novel Actor in the Emotional-Like Responses 英文参考文献.doc

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GPR3 Receptor, a Novel Actor in the Emotional-Like Responses 英文参考文献

GPR3Receptor,aNovelActorintheEmotional-Like Responses OlgaValverde1,EvelyneCe′le′rier2,Ma′riaBaranyi3,PierreVanderhaeghen4,RafaelMaldonado2 ,Beata Sperlagh3,GilbertVassart4,CatherineLedent4* 1GrupdeRecercadeNeurobiologiadelComportament,DepartamentdeCie`nciesExperimentalsidelaSalut,UniversitatPompeuFabra,Barcelona,Spain,2Laboratoride Neurofarmacologia,DepartamentdeCie`nciesExperimentalsidelaSalut,UniversitatPompeuFabra,Barcelona,Spain,3InstituteofExperimentalMedicine,Hungarian AcademyofSciences,Budapest,Hungary,4IRIBHM,Universite′ LibredeBruxelles(ULB),CampusErasme,Brussels,Belgium Abstract GPR3isanorphanGprotein-coupledreceptorendowedwithconstitutiveGssignalingactivity,whichisexpressedbroadly inthecentralnervoussystem,withmaximalexpressioninthehabenula.Weinvestigatedtheconsequencesofitsgenetic deletion in several behavioral paradigms and on neurotransmission. Compared to wild-type, hippocampal neurons from Gpr32/2 mice displayed lower basal intracellular cAMP levels, consistent with the strong constitutive activity of GPR3 in transientlytransfectedcells.BehavioralanalysesrevealedthatGpr32/2miceexhibitedahighlevelofavoidanceofnoveland unfamiliarenvironment,associatedwithincreasedstressreactivityinbehavioraldespairparadigmsandaggressivebehavior intheresident-intrudertest.Onthecontrary,nodeficitwasfoundinthelearningabilitytoavoidanaversiveeventinactive avoidancetask.ThereducedabilityofGpr32/2micetocopewithstresswasunrelatedtodysfunctionofthehypothalamic- pituitary-adrenalaxis,withGpr32/2miceshowingnormalcorticosteroneproductionunderbasalorstressfulconditions.In contrast, dramatic alterations of monoamine contents were found in hippocampus, hypothalamus and frontal cortex of Gpr32/2mice.OurresultsestablishalinkbetweentonicstimulationofthecAMPsignalingpathwaybyGPR3andcontrolof neurotransmission by monoamines throughout the forebrain. GPR3 qualifies as a new player in the modulation of behavioral responses to stress and constitutes a novel promising pharmacological t