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Dopamine-Induced Plasticity, Phospholipase D (PLD) Activity and Cocaine-Cue Behavior Depend on PLD-Linked Metabotropic Glutamate Receptors in Amygdala 英文参考文献.docVIP

Dopamine-Induced Plasticity, Phospholipase D (PLD) Activity and Cocaine-Cue Behavior Depend on PLD-Linked Metabotropic Glutamate Receptors in Amygdala 英文参考文献.doc

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Dopamine-Induced Plasticity, Phospholipase D (PLD) Activity and Cocaine-Cue Behavior Depend on PLD-Linked Metabotropic Glutamate Receptors in Amygdala 英文参考文献

Dopamine-InducedPlasticity,PhospholipaseD(PLD) ActivityandCocaine-CueBehaviorDependonPLD- LinkedMetabotropicGlutamateReceptorsinAmygdala BalajiKrishnan1.*,KathyM.Genzer1.,SebastianW.Pollandt1,JieLiu1,2,JoelP.Gallagher1 ,Patricia Shinnick-Gallagher1 1Department of Pharmacology and Toxicology, University of Texas Medical Branch at Galveston, Galveston, Texas, United States of America, 2Department of Anesthesiology,PresbyterianHospital,ColumbiaUniversity,NewYork,NewYork,UnitedStatesofAmerica Abstract Cocaine-cueassociationsinducesynapticplasticitywithlonglastingmolecularandcellularchangesintheamygdala,asite crucial for cue-associated memory mechanisms. The underlying neuroadaptations can include marked alterations in signalingviadopamine(DA)receptors(DRs)andmetabotropicglutamate(Glu)receptors(mGluRs).Previously,wereported that DR antagonists blocked forms of synaptic plasticity in amygdala slices of Sprague-Dawley rats withdrawn from repeatedcocaineadministration.Inthepresentstudy,weinvestigatedsynapticplasticityinducedbyexogenousDAandits dependenceonmGluRsignalingandapotentialroleforphospholipaseD(PLD)asadownstreamelementlinkedtomGluR andDRsignaling.Utilizingamodifiedconditionedplacepreference(CPP)paradigmasafunctionalbehavioralmeasure,we studied the neurophysiological effects after two-weeks to the last cocaine conditioning. We recorded, electrophysiolog- ically, a DR-induced synaptic potentiation in the basolateral to lateral capsula central amygdala (BLA-lcCeA) synaptic pathwaythatwasblockedbyantagonistsofgroupImGluRs,particularly,thePLD-linkedmGluR.Inaddition,weobserved 2–2.5foldincreaseinPLDexpressionand3.7-foldincreaseinbasalPLDenzymeactivity.TheenhancedPLDactivitycouldbe furtherstimulated(9.3fold)byaDAD1-like(D1/5R)receptoragonist,anddecreasedtocontrollevelsbymGluR1andPLD- linked mGluRantagonists. DiminishedCPP wasobservedby infusionof aPLD-linkedmGluRantagonist, PCCG-13,in the amygdala15minutespriortotesting,twoweeksafterthelastcocaineinjection.Theseresul

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