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
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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that DR antagonists blocked forms of synaptic plasticity in amygdala slices of Sprague-Dawley rats withdrawn from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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