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1、29Tachykininregulationofcholinergictransmissioninthelimbic/prefrontalterritoryoftheratdorsalstriatum:implicationofnewneurokinine1-sensitivereceptorbindingsiteandinteractionwithenkephalin/muopioidreceptortransmissionSylviePérez,AdrienneTierney,Jean-MichelDeniau,andMarie-Louis
2、eKemelINSERM,U667,CollègedeFrance,Paris,F-75231France ;UnivPierreetMarieCurie,Paris,F-75005,France.Tel:(33)0144271216Fax:(33)0144271260Correspondingauthor:Marie-LouiseKemelINSERMU667,CollègedeFrance,11placeMarcelinBerthelot75231Paris,France;e-mail:marie-lou.kemel@college-de-
3、france.frAbbreviation:a-methyl-p-tyrosine,aMPT;bfunaltrexamine,bFNA ;acetylcholine,ACh ;cholineacetyltransferase,ChAT ;dopamine,DA ;enkephalin,ENK ;muopioidreceptor,MOR ;neurokinin,NK;NK1receptor,NK1R ;prefrontal,PF ;substanceP,SP,29ABSTRACTThetachykininneurokinin1receptors(
4、NK1Rs)regulationofacetylcholinereleaseanditsinteractionwiththeenkephalin/muopioidreceptors(MORs)transmissionwasinvestigatedinthelimbic/prefrontalterritoryofthedorsalstriatum.Usingdoubleimmunohistochemistry,wefirstshowedthatinthisterritory,cholinergicinterneuronscontaintachyk
5、ininNK1Rsandco-expressMORsinthelastpartofthelightperiod(afternoon).Inslicesofthestriatallimbic/prefrontalterritory,followingsuppressionofthedopaminergicinhibitorycontrolofacetylcholinerelease,applicationofthetachykininNK1Rantagonist,SSR240600,markedlyreducedtheNMDA-inducedac
6、etylcholinereleaseinthemorningbutnotintheafternoonwhentheenkephalin/MORregulationisoperational.Intheafternoon,theNK1Rantagonistresponserequiredthesuppressionoftheenkephalin/MORinhibitorycontrolofacetylcholinereleasebybfunaltrexamine.ThepharmacologicalprofileofthetachykininNK
7、1Rregulationtestedbyapplicationofthereceptoragonists([Pro9]substanceP,neurokininA,neuropeptideKandsubstanceP(6-11))andantagonists(SSR240600,GR205171,GR82334andRP67580)indicatedthatthesubtypeoftachykininNK1RimplicatedarethenewNK1-sensitivereceptorbindingsite.Therefore,intheli
8、mbic/prefrontalterritoryofthedorsalstriatum,endogenoustachykininfacilitates
