NMDA Receptors on Non-Dopaminergic Neurons in the VTA Support Cocaine Sensitization 英文参考文献.docVIP

NMDA Receptors on Non-Dopaminergic Neurons in the VTA Support Cocaine Sensitization 英文参考文献.doc

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NMDA Receptors on Non-Dopaminergic Neurons in the VTA Support Cocaine Sensitization 英文参考文献

NMDAReceptorsonNon-DopaminergicNeuronsinthe VTASupportCocaineSensitization YuLuo1.,CameronH.Good1.,OscarDiaz-Ruiz1,YaJunZhang1,AlexanderF.Hoffman1,LufeiShan1, SerenaY.Kuang1,NasirMalik1,VladimirI.Chefer2,AndreasC.Tomac1¤,CarlR.Lupica1,CristinaM. Ba¨ckman1* 1Cellular Neurobiology Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States of America, 2Behavioral NeuroscienceBranch,NationalInstituteonDrugAbuse,NationalInstitutesofHealth,Baltimore,Maryland,UnitedStatesofAmerica Abstract Background:TheinitiationofbehavioralsensitizationtococaineandotherpsychomotorstimulantsisthoughttoreflectN- methyl-D-aspartate receptor (NMDAR)-mediated synaptic plasticity in the mesolimbic dopamine (DA) circuitry. The importanceofdruginducedNMDARmediatedadaptationsinventraltegmentalarea(VTA)DAneurons,anditsassociation with drug seeking behaviors, has recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons expressingCrerecombinaseunderthecontroloftheendogenousdopaminetransportergene(NR1DATCre mice). MethodologyandPrincipalFindings:UsinganadditionalNR1DATCre mousetransgenicmodel,wedemonstratethatwhile the selective inactivation of NMDARs in DA neurons eliminates the induction of molecular changes leading to synaptic strengthening, behavioral measures such as cocaine induced locomotor sensitization and conditioned place preference remainintactinNR1DATCremice.SinceVTADAneuronsprojectingtotheprefrontalcortexandamygdalaexpresslittleorno detectablelevelsofthedopaminetransporter,ithasbeenspeculatedthatNMDAreceptorsinDAneuronsprojectingto thesebrainareasmayhavebeensparedinNR1DATCremice.HerewedemonstratethattheNMDAreceptorgeneisablatedin themajorityofVTADAneurons,includingthoseexhibitingundetectableDATexpressionlevelsinourNR1DATCre transgenic model, and that application of an NMDAR antagonist within the VTA of NR1DATCre animals still blocks sensitization to cocaine. Conclusions/Significance: Theseresults elim

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