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 ResearchConceptsPosttraumatic 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
Local Application of Neurotrophins Specifies Axons Through Inositol 1,4,5-Trisphosphate, Calcium, and Ca2+/Calmodulin–Dependent Protein Kinases
Nakamuta S, Funahashi Y, Namba T, Arimura N, Picciotto MR, Tokumitsu H, Soderling TR, Sakakibara A, Miyata T, Kamiguchi H, Kaibuchi K. Local Application of Neurotrophins Specifies Axons Through Inositol 1,4,5-Trisphosphate, Calcium, and Ca2+/Calmodulin–Dependent Protein Kinases. Science Signaling 2011, 4: ra76. PMID: 22087032, DOI: 10.1126/scisignal.2002011.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorNeurotrophin-3Neurotrophin brain-derived neurotrophic factorLocal applicationImmature neuritesCultured hippocampal neuronsAxon specificationSpecific intracellular pathwaysNeurotrophic factorCortical neuronsHippocampal neuronsNeurotrophin receptorParacrine fashionCultured neuronsDependent protein kinase kinaseDependent protein kinaseNeuronsProtein kinase kinaseAxonsIntracellular pathwaysDependent fashionLocal activationNeuritesNeurite outgrowthGrowth conesFACS 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 antibodiesBrainTissueGenesDecreased α4β2 nicotinic receptor number in the absence of mRNA changes suggests post‐transcriptional regulation in the spontaneously hypertensive rat model of ADHD
Wigestrand MB, Mineur YS, Heath CJ, Fonnum F, Picciotto MR, Walaas SI. Decreased α4β2 nicotinic receptor number in the absence of mRNA changes suggests post‐transcriptional regulation in the spontaneously hypertensive rat model of ADHD. Journal Of Neurochemistry 2011, 119: 240-250. PMID: 21824140, PMCID: PMC3171636, DOI: 10.1111/j.1471-4159.2011.07415.x.Peer-Reviewed Original ResearchMeSH KeywordsAconitineAnimalsAttention Deficit Disorder with HyperactivityAzetidinesBrain ChemistryBridged Bicyclo Compounds, HeterocyclicBungarotoxinsIn Vitro TechniquesKineticsMaleMembranesNicotinic AgonistsNicotinic AntagonistsProtein Processing, Post-TranslationalPyridinesRatsRats, Inbred SHRRats, Inbred WKYReceptors, NicotinicReverse Transcriptase Polymerase Chain ReactionRNA, MessengerThermodynamicsConceptsAttention-deficit/hyperactivity disorderQuantitative real-time PCRBrain regionsCerebellum of SHRWistar-Kyoto rat controlsHypertensive rat modelMRNA levelsNicotinic receptor numbersCentral nicotinic receptorsSpecific brain regionsAdditional brain regionsSHR brainHypertensive ratsRat modelReal-time PCRNicotinic receptorsReceptor numberEpidemiological studiesLevels of mRNAΑ4β2 nAChRsSHRWKYNAChRsHyperactivity disorderStrain differencesFACS 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
2010
MicroRNA knocks down cocaine
Picciotto MR. MicroRNA knocks down cocaine. Nature 2010, 466: 194-195. PMID: 20613832, DOI: 10.1038/466194a.Peer-Reviewed Original Research
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 mechanismsAntidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression
Vieyra-Reyes P, Mineur YS, Picciotto MR, Túnez I, Vidaltamayo R, Drucker-Colín R. Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression. Brain Research Bulletin 2008, 77: 13-18. PMID: 18582540, PMCID: PMC2771408, DOI: 10.1016/j.brainresbull.2008.05.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBehavior, AnimalDepressionDisease Models, AnimalDrug Administration ScheduleExploratory BehaviorInjections, IntraperitonealMaleMotor ActivityNicotineOlfactory BulbPsychology, ComparativeRatsRats, Long-EvansRats, WistarSelf AdministrationSpecies SpecificitySwimmingTranscranial Magnetic StimulationConceptsDepression-like symptomsTranscranial magnetic stimulationAntidepressant-like effectsWistar ratsMagnetic stimulationOlfactory bulbectomyRat strainsDaily transcranial magnetic stimulationOlfactory bulbectomy rat modelEffects of nicotineOral nicotine intakeOral intakeDepression managementSwim testTherapeutic alternativeNicotine intakeRat modelLong-Evans rat strainDepression susceptibilitySymptomsLong-EvansNicotineInnate differencesRatsBulbectomy
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 ResearchConceptsVentral 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 modelA Calcium- and Calmodulin-Dependent Kinase Iα/Microtubule Affinity Regulating Kinase 2 Signaling Cascade Mediates Calcium-Dependent Neurite Outgrowth
Uboha NV, Flajolet M, Nairn AC, Picciotto MR. A Calcium- and Calmodulin-Dependent Kinase Iα/Microtubule Affinity Regulating Kinase 2 Signaling Cascade Mediates Calcium-Dependent Neurite Outgrowth. Journal Of Neuroscience 2007, 27: 4413-4423. PMID: 17442826, PMCID: PMC6672303, DOI: 10.1523/jneurosci.0725-07.2007.Peer-Reviewed Original ResearchConceptsKinase domainNeurite outgrowthNeuronal differentiationCalmodulin-dependent kinase ITwo-hybridNeuro-2a cellsPhosphorylation sitesSignal transductionKinase ICaMKIKinase activityMicrotubule affinityKinase 2Calcium-dependent pathwayCritical regulatorIndependent screensPrimary hippocampal neuronsNovel siteCalcium ionophore ionomycinOutgrowthIonophore ionomycinSynaptic plasticityDifferentiationHippocampal neuronsPhysiological effects
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 scheduleGalanin and galanin‐like peptide modulate neurite outgrowth via protein kinase C‐mediated activation of extracellular signal‐related kinase
Hawes JJ, Narasimhaiah R, Picciotto MR. Galanin and galanin‐like peptide modulate neurite outgrowth via protein kinase C‐mediated activation of extracellular signal‐related kinase. European Journal Of Neuroscience 2006, 23: 2937-2946. PMID: 16819983, DOI: 10.1111/j.1460-9568.2006.04828.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell DifferentiationCells, CulturedDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEnzyme ActivationEnzyme InhibitorsExtracellular Signal-Regulated MAP KinasesGalaninGalanin-Like PeptideNeuritesNeuronsProtein Kinase CRatsReceptors, GalaninReverse Transcriptase Polymerase Chain ReactionRNA, MessengerStem CellsConceptsGalanin-like peptideProtein kinase CNervous systemNeurite outgrowthAdult hippocampal progenitor cellsAbility of galaninKinase CERK phosphorylationHippocampal progenitor cellsNeuronal cell line PC12Central nervous systemModulates Neurite OutgrowthExtracellular signal-related kinase (ERK) phosphorylationConcentration-dependent mannerNerve injuryNeuropeptide galaninNeurotrophic effectsExtracellular signal-related kinaseReceptor subtypesNovel physiological roleAdult brainGalaninCell line PC12Signal-related kinaseProgenitor cells
2004
Cytoplasmic localization of calcium/calmodulin‐dependent protein kinase I‐α depends on a nuclear export signal in its regulatory domain
Stedman DR, Uboha NV, Stedman TT, Nairn AC, Picciotto MR. Cytoplasmic localization of calcium/calmodulin‐dependent protein kinase I‐α depends on a nuclear export signal in its regulatory domain. FEBS Letters 2004, 566: 275-280. PMID: 15147908, DOI: 10.1016/j.febslet.2004.04.042.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 1Calcium-Calmodulin-Dependent Protein KinasesConsensus SequenceCytoplasmEnzyme ActivationKaryopherinsMicroscopy, FluorescenceNuclear Localization SignalsPC12 CellsProtein Structure, TertiaryRatsReceptors, Cytoplasmic and NuclearRecombinant Fusion ProteinsSubcellular FractionsTransfectionConceptsNuclear export signalExport signalRegulatory domainCytoplasmic localizationCalmodulin-dependent protein kinase ICalcium/calmodulin-dependent protein kinase IRev-like nuclear export signalProtein kinase IUbiquitous cytosolic enzymeCalcium/calmodulinTranscriptional regulationNuclear exportKinase INuclear proteinsNuclear entryCatalytic coreCytosolic enzymeI alphaSequenceCRM1VitroMutantsLocalizationCalmodulinDomain
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