Assessment of 5-HT7 Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice英文文献资料.docVIP

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Assessment of 5-HT7 Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice英文文献资料.doc

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Assessment of 5-HT7 Receptor Agonists Selectivity Using Nociceptive and Thermoregulation Tests in Knockout versus Wild-Type Mice英文文献资料

HindawiPublishingCorporation AdvancesinPharmacologicalSciences Volume2012,ArticleID312041,9pages doi:10.1155/2012/312041 ResearchArticle Assessmentof5-HT7ReceptorAgonistsSelectivity UsingNociceptiveandThermoregulationTestsinKnockout versusWild-TypeMice AlexBrenchat, 1 MariaRocasalbas, DanielZamanillo, MichelHamon, 1 1 2 andLuzRomero 1 Jos′eMiguelVela, 1 1 2 DepartmentofPharmacology,DrugDiscoveryandPreclinicalDevelopment,ESTEVE,AvenidaMaredeD′eudeMontserrat221, 08041Barcelona,Spain UMR894INSERM-CPN/UPMC,Facult′edeM′edecinePierreetMarieCurie,SitePiti′e-Salp?etri`ere,91boulevarddel’H?opital, 75634ParisCedex13,France CorrespondenceshouldbeaddressedtoLuzRomero,lromero@esteve.es Received17February2012;Accepted27April2012 AcademicEditor:KarimA.Alkadhi Copyright?2012AlexBrenchatetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. Nostudyhaseverexaminedthee?ectof5-HT7receptoragonistsonnociceptionbyusing5-HT7receptorknockoutmice.Basal sensitivitytonoxiousheatstimuliandformalin-inducednociceptioninbothphaseIandIIoftheformalintestdidnotdi?erin5- HT7receptorknockoutmiceandpairedwild-typecontrols.Similarly,therewasnosigni?cantdi?erenceinbasalbodytemperature betweenbothgenotypes.Subcutaneousadministrationof5-HT7receptoragonistsAS-19(10mg/kg),E-57431(10mg/kg),andE- 55888(20mg/kg)signi?cantlyreducedformalin-inducedlicking/bitingbehaviorduringthephaseIIofthetestinwild-typebut notin5-HT7receptorknockoutmice.Attheseactiveanalgesicdoses,noneofthethree5-HT7receptoragonistsmodi?edthebasal bodytemperatureneitherinwild-typenorin5-HT7receptorknockoutmice.However,asigni?cantdecreaseinbodytemperature wasobservedatahigherdose(20mg/kg)ofAS-19andE-57431inbothgenotypes.Ourdatastronglysuggestthatthe5-HT7 receptoragonistsAS-19,E-57431,andE-55888produceantinociceptionintheformalintestbyactivating5-HT7receptors.These resultsalso