2022
Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsExtinction, PsychologicalFearMaleMicePrefrontal CortexRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale mice
2018
Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons
Li D, Musante V, Zhou W, Picciotto MR, Nairn AC. Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons. Journal Of Biological Chemistry 2018, 293: 11179-11194. PMID: 29802198, PMCID: PMC6052221, DOI: 10.1074/jbc.ra117.001519.Peer-Reviewed Original ResearchConceptsSerine/threonine phosphatase PP2AStriatin-interacting phosphataseRNA knockdown approachB subunitSTRIPAK complexPhosphatase PP2AProtein phosphataseMultiprotein complexesKnockdown approachStriatin familyMutant constructsStriatal neuronal culturesPP2ANeuronal developmentPrimary striatal neuronal culturesDendritic phenotypeKnockdown modelSynapse formationSubunitsSpine developmentSelective roleReduced expressionNeuron maturationNeuronal culturesStriatal neurons
2015
DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons
Engmann O, Giralt A, Gervasi N, Marion-Poll L, Gasmi L, Filhol O, Picciotto MR, Gilligan D, Greengard P, Nairn AC, Hervé D, Girault JA. DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons. Nature Communications 2015, 6: 10099. PMID: 26639316, PMCID: PMC4675091, DOI: 10.1038/ncomms10099.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBrainCaffeineCalmodulin-Binding ProteinsCentral Nervous System StimulantsChlorocebus aethiopsCocaineCOS CellsDendritic SpinesDopamine and cAMP-Regulated Phosphoprotein 32EnvironmentFluorescence Recovery After PhotobleachingImmunoblottingImmunohistochemistryIn Vitro TechniquesMass SpectrometryMiceMice, Inbred C57BLMutationNeostriatumNeuronsNucleus AccumbensPhosphorylationRatsRats, Sprague-DawleyRewardConceptsAdducin phosphorylationCytoskeletal proteinsActin filamentsMolecular pathwaysCellular mechanismsEnvironmental changesPhosphorylationDARPP-32Striatal neuronsAdducinMutant miceSynaptic stabilityProteinCascadeMultiple effectsEnvironmental effectsBindsDendritic spinesNeuronsModification of responsesBrief exposurePathwayInteractionFilamentsEnrichment
2013
Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule
Peng C, Stokes C, Mineur YS, Picciotto MR, Tian C, Eibl C, Tomassoli I, Guendisch D, Papke RL. Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule. Journal Of Pharmacology And Experimental Therapeutics 2013, 347: 424-437. PMID: 23959137, PMCID: PMC3807070, DOI: 10.1124/jpet.113.206904.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAzocinesBehavior, AnimalBenzazepinesBrainBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugDrug Partial AgonismHEK293 CellsHumansMaleMembrane PotentialsMiceMolecular StructureNicotinic AgonistsOocytesPatch-Clamp TechniquesQuinolizinesQuinoxalinesRatsRats, Sprague-DawleyReceptors, NicotinicTobacco Use DisorderVareniclineXenopus laevisConceptsPartial agonistLGN neuronsMouse tail suspension testLateral geniculate nucleus neuronsNicotinic acetylcholine receptor functionPartial agonist therapiesTail suspension testStratum radiatum interneuronsSmoking cessation drugNicotinic partial agonistAcetylcholine receptor functionHuman embryonic kidney 293 cellsSteady-state activationAgonist therapyRadiatum interneuronsEmbryonic kidney 293 cellsCessation drugsNucleus neuronsSuspension testΑ7 currentsNicotine addictionSide effectsVareniclineΑ4β2 nAChRsSR interneurons
2011
FACS purification of immunolabeled cell types from adult rat brain
Guez-Barber D, Fanous S, Harvey BK, Zhang Y, Lehrmann E, Becker KG, Picciotto MR, Hope BT. FACS purification of immunolabeled cell types from adult rat brain. Journal Of Neuroscience Methods 2011, 203: 10-18. PMID: 21911005, PMCID: PMC3221768, DOI: 10.1016/j.jneumeth.2011.08.045.Peer-Reviewed Original ResearchConceptsFluorescence-activated cell sortingCell typesPromoter-driven reporter geneBrain tissueExtracellular proteinsFACS procedureReporter geneFACS purificationRat brainReal-time PCRMolecular analysisSorted cellsCell sortingAdult rat brainTime PCRIntact cell bodiesTransgenic miceMolecular alterationsNeuN antibodyQuantitative assayCell bodiesAvailable antibodiesBrainTissueGenesFACS Identifies Unique Cocaine-Induced Gene Regulation in Selectively Activated Adult Striatal Neurons
Guez-Barber D, Fanous S, Golden SA, Schrama R, Koya E, Stern AL, Bossert JM, Harvey BK, Picciotto MR, Hope BT. FACS Identifies Unique Cocaine-Induced Gene Regulation in Selectively Activated Adult Striatal Neurons. Journal Of Neuroscience 2011, 31: 4251-4259. PMID: 21411666, PMCID: PMC3073079, DOI: 10.1523/jneurosci.6195-10.2011.Peer-Reviewed Original ResearchConceptsStriatal neuronsFluorescence-activated cell sortingNeural activity marker FosCocaine-induced locomotionActivity marker FosAdult striatal neuronsUnique gene expression profileP38 MAPK signalingCell-type specificityGene expression profilesSmall proportionTransgenic ratsActivated neuronsImmediate early genesMolecular neuroadaptationsSpecific neuronsGene regulationBehavioral effectsNeuronsAbused drugsMAPK signalingExpression profilesProtein productsCocaineLacZ gene
2008
Administration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats
Addy NA, Bahi A, Taylor JR, Picciotto MR. Administration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats. Psychopharmacology 2008, 200: 129-139. PMID: 18587562, PMCID: PMC2574760, DOI: 10.1007/s00213-008-1189-5.Peer-Reviewed Original ResearchConceptsLocomotor responseCocaine 5Cocaine injectionLocomotor activityCocaine-induced locomotor activityAcute locomotor responseAcute cocaine challengeMale Sprague-DawleyCocaine-mediated behaviorsCyclosporine administrationMethodsLocomotor activityCalcineurin inhibitorsDaily administrationI. AdministrationCocaine challengeCocaine exposureSprague-DawleyCyclosporine pretreatmentAbility of calcineurinConclusionOur resultsCocaine-mediated changesAdministrationCocaineSynapsin IPotential mechanisms
2007
Role of Calcineurin in Nicotine-Mediated Locomotor Sensitization
Addy NA, Fornasiero EF, Stevens TR, Taylor JR, Picciotto MR. Role of Calcineurin in Nicotine-Mediated Locomotor Sensitization. Journal Of Neuroscience 2007, 27: 8571-8580. PMID: 17687035, PMCID: PMC6672935, DOI: 10.1523/jneurosci.2601-07.2007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcineurinCalcineurin InhibitorsCyclosporineMaleMotor ActivityNicotineRatsRats, Sprague-DawleyVentral Tegmental AreaConceptsVentral tegmental areaEffects of nicotineLocomotor sensitizationCalcineurin inhibitorsRole of calcineurinInfusion of rapamycinCultured cortical neuronsSprague-Dawley ratsNicotine-mediated behaviorsCyclosporine administrationTegmental areaCortical neuronsDawley ratsFK-binding proteinActivation of calcineurinNicotineSensitizationCalcineurin activityInfusionIntracellular signalingAdministrationCalcineurinFK506InhibitorsDirect infusionPrenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors
Elsworth JD, Morrow BA, Nguyen V, Mitra J, Picciotto MR, Roth RH. Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors. Neuroscience 2007, 147: 419-427. PMID: 17543464, PMCID: PMC2855228, DOI: 10.1016/j.neuroscience.2007.04.036.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoradiographyAutoreceptorsClonidineCocaineFemaleGenes, fosImmunohistochemistryInjections, IntravenousLocus CoeruleusMaleNeuronsNorepinephrinePrefrontal CortexPregnancyPrenatal Exposure Delayed EffectsRadioligand AssayRatsRats, Sprague-DawleyStress, PsychologicalTyrosine 3-MonooxygenaseConceptsPrenatal cocaine exposureNorepinephrine neuronsCocaine exposurePrenatal cocaineTyrosine hydroxylase-positive neuronsLocus coeruleus norepinephrine neuronsPrenatal cocaine exposure resultsPrenatal saline controlsRole of autoreceptorsLocus coeruleus noradrenergic systemPrenatal treatment groupsCocaine exposure resultsAlpha2-adrenergic receptorsInjection of cocaineGestational day 10Pharmacology of cocaineDaily i.LC neuronsNorepinephrine turnoverPregnant ratsNeurobehavioral deficitsSaline controlsFos expressionNoradrenergic systemRat model
2006
Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats
Lynch WJ, Kiraly DD, Caldarone BJ, Picciotto MR, Taylor JR. Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats. Psychopharmacology 2006, 191: 263-271. PMID: 17180335, DOI: 10.1007/s00213-006-0656-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternCocaineCyclic AMP-Dependent Protein KinasesDopamine and cAMP-Regulated Phosphoprotein 32Dopamine Uptake InhibitorsFemaleMaleNucleus AccumbensPhosphorylationRatsRats, Sprague-DawleyReceptors, AMPASelf AdministrationSex FactorsSignal TransductionSubstance Withdrawal SyndromeGhrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal Of Clinical Investigation 2006, 116: 3229-3239. PMID: 17060947, PMCID: PMC1618869, DOI: 10.1172/jci29867.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAppetiteDopamineFluorescent Antibody TechniqueGhrelinMaleMesencephalonMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPatch-Clamp TechniquesPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsVentral Tegmental AreaConceptsVentral tegmental areaGHSR-deficient miceGHSR-dependent mannerGut hormone ghrelinDopamine neuronal activityMidbrain dopamine neuronsMesolimbic reward circuitrySynaptic input organizationPeripheral ghrelinRebound feedingVTA administrationOrexigenic effectDopamine turnoverGHSR antagonistDopamine neuronsHypothalamic centersTegmental areaHormone ghrelinNucleus accumbensGhrelinNeuronal activitySynapse formationReward circuitryInput organizationFeeding schedule
2003
Nicotine Induces Glutamate Release from Thalamocortical Terminals in Prefrontal Cortex
Lambe EK, Picciotto MR, Aghajanian GK. Nicotine Induces Glutamate Release from Thalamocortical Terminals in Prefrontal Cortex. Neuropsychopharmacology 2003, 28: 216-225. PMID: 12589374, DOI: 10.1038/sj.npp.1300032.Peer-Reviewed Original ResearchConceptsPrefrontal cortexSpontaneous excitatory postsynaptic currentsPrefrontal cortical activationEmotional cuesHigh-affinity nicotinic receptorsCognitive functionCortical activationThalamocortical terminalsGlutamate releaseBrain regionsLayer V pyramidal neuronsCognitionPrefrontal cortical slicesExcitatory postsynaptic currentsRelease of glutamateCortexStimulation of nAChRsNicotinic acetylcholine receptorsΑ4β2 nAChRsDifferent neurotransmittersCerebral cortexPyramidal neuronsCortical slicesPostsynaptic currentsΜ-opioid
2002
Acute and long‐term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections
Ferrari R, Le Novère N, Picciotto MR, Changeux JP, Zoli M. Acute and long‐term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections. European Journal Of Neuroscience 2002, 15: 1810-1818. PMID: 12081661, DOI: 10.1046/j.1460-9568.2001.02009.x.Peer-Reviewed Original ResearchMeSH KeywordsAmphetamineAnimalsDopamineDopamine Plasma Membrane Transport ProteinsDrug Administration RoutesExtracellular SpaceHabituation, PsychophysiologicMaleMembrane GlycoproteinsMembrane Transport ProteinsMicrodialysisMotor ActivityNerve Tissue ProteinsNeural PathwaysNeuronal PlasticityNicotineNucleus AccumbensPresynaptic TerminalsRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateRNA, MessengerSubstance-Related DisordersTime FactorsTyrosine 3-MonooxygenaseVentral Tegmental AreaConceptsDialysate DA levelsGluR1 mRNA levelsSingle nicotine injectionNicotine administrationDA levelsMesolimbic dopamine pathwayNicotine injectionTyrosine hydroxylaseDopamine pathwayMRNA levelsBasal DA levelsExtracellular DA levelsMesolimbic DA pathwaySystemic intraperitoneal injectionTH mRNA levelsIntra-accumbens infusion
2001
Effects of nicotine pretreatment on dopaminergic and behavioral responses to conditioned fear stress in rats: dissociation of biochemical and behavioral effects
George T, Picciotto M, Verrico C, Roth R. Effects of nicotine pretreatment on dopaminergic and behavioral responses to conditioned fear stress in rats: dissociation of biochemical and behavioral effects. Biological Psychiatry 2001, 49: 300-306. PMID: 11230881, DOI: 10.1016/s0006-3223(00)00928-8.Peer-Reviewed Original ResearchConceptsConditioned fear stressNicotine pretreatmentMedial prefrontal cortexFear stressDopamine metabolismNucleus accumbensPrefrontal cortexAcute footshock stressImmobility responseBehavioral responsesCortical dopaminergicDopamine utilizationCortical dopamineNicotine exposureFootshock stressNicotine dependenceAnxiolytic activityConditioned fear paradigmNicotine differsDay 21Psychological stressorsBehavioral effectsDopaminergicClinical contextPreferential activation
2000
Nicotinic modulation of mesoprefrontal dopamine neurons: pharmacologic and neuroanatomic characterization.
George TP, Verrico CD, Picciotto MR, Roth RH. Nicotinic modulation of mesoprefrontal dopamine neurons: pharmacologic and neuroanatomic characterization. Journal Of Pharmacology And Experimental Therapeutics 2000, 295: 58-66. PMID: 10991961.Peer-Reviewed Original ResearchConceptsMesoprefrontal DA neuronsDA neuronsLocal infusionNicotinic acetylcholine receptor stimulationMesoprefrontal dopamine neuronsMesoprefrontal dopamine systemEndogenous opioid peptidesVentral tegmental areaHigh comorbid ratesNicotine-pretreated ratsMedial prefrontal cortexDA metabolismNicotinic modulationCortical dysfunctionNicotine administrationCigarette smokingSite of actionStress-induced statesNicotine pretreatmentDA dysregulationDopamine neuronsSystemic administrationTegmental areaDA dysfunctionCognitive dysfunctionThe Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway
Paul S, Snyder G, Yokakura H, Picciotto M, Nairn A, Lombroso P. The Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway. Journal Of Neuroscience 2000, 20: 5630-5638. PMID: 10908600, PMCID: PMC6772528, DOI: 10.1523/jneurosci.20-15-05630.2000.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalytic DomainCorpus StriatumCyclic AMP-Dependent Protein KinasesEnzyme ActivationIn Vitro TechniquesMaleMolecular Sequence DataNeuronsPhosphoproteinsPhosphorus RadioisotopesPhosphorylationProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, Dopamine D1Signal TransductionConceptsProtein tyrosine phosphatase familyCAMP-dependent protein kinaseTryptic phosphopeptide mappingPotential phosphorylation sitesUnique N-terminalProtein-protein interactionsMembrane-associated proteinsRole of phosphorylationTyrosine phosphatase familyAmino acid sequenceSite-directed mutagenesisAmino acid sequencingPKA-dependent pathwayTyrosine phosphatase STEPPhosphatase familyPhosphopeptide mappingPhosphorylation sitesAlternative splicingSubcellular compartmentsProtein kinaseTerminal domainEquivalent residuesCytosolic proteinsSpecific residuesAcid sequence5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors
Mukhin A, Gündisch D, Horti A, Koren A, Tamagnan G, Kimes A, Chambers J, Vaupel D, King S, Picciotto M, Innis R, London E. 5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors. Molecular Pharmacology 2000, 57: 642-649. PMID: 10692507, DOI: 10.1124/mol.57.3.642.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAlpha4beta2 nAChRsAcetylcholine receptorsNeuronal nicotinic acetylcholine receptorsAffinity of epibatidineRat adrenal glandMuscle-type nAChRsSubtype-selective ligandsAlpha4beta2 subtypeAdrenal glandRat brainSelective radioligandBrain regionsNAChRsBeta4 subunitsRadioiodinated ligandBeta2 subunitVivo studiesEpibatidineVivo experimentsHuman brainSubtypesRadioligandBrainReceptors