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
2014
Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons
Mazei-Robison MS, Appasani R, Edwards S, Wee S, Taylor SR, Picciotto MR, Koob GF, Nestler EJ. Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons. PLOS ONE 2014, 9: e95962. PMID: 24755634, PMCID: PMC3995955, DOI: 10.1371/journal.pone.0095962.Peer-Reviewed Original ResearchConceptsVentral tegmental areaSoma sizeDopamine neuronsVentral tegmental area dopamine neuronsChronic opiate administrationAdditional drug classesDrug-specific mannerMorphological changesSelf-administer cocaineOpiate administrationTegmental areaDrug classesDA circuitsMesolimbic DA circuitSelf-AdministrationFiring rateSimilar morphological changesGeneral hallmarkNeuronsNicotineCocaineDrugsRecent findingsPrevious observationsNeuroplasticity
2013
An indirect resilience to addiction
Picciotto MR. An indirect resilience to addiction. Nature Neuroscience 2013, 16: 521-523. PMID: 23619754, DOI: 10.1038/nn.3375.Peer-Reviewed Original ResearchRepeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in mice
Rao Y, Mineur YS, Gan G, Wang AH, Liu Z, Wu X, Suyama S, de Lecea L, Horvath TL, Picciotto MR, Gao X. Repeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in mice. The Journal Of Physiology 2013, 591: 1951-1966. PMID: 23318871, PMCID: PMC3624862, DOI: 10.1113/jphysiol.2012.246983.Peer-Reviewed Original ResearchConceptsCAMP response element-binding proteinHypocretin neuronsLong-term potentiationSynaptic potentiationLateral hypothalamusCocaine administrationExperience-dependent synaptic potentiationExperience-dependent potentiationHypocretin-producing neuronsVivo cocaine administrationCocaine-treated animalsOrexin-producing neuronsAMPA-type glutamate receptorsVentral tegmental areaHigh-frequency stimulationCocaine-treated micePlace preference protocolResponse element-binding proteinDrugs of abuseCocaine withdrawalTegmental areaGlutamatergic synapsesGlutamate receptorsHypocretin systemElement-binding protein
2012
The Synaptic Adhesion Molecule SynCAM 1 Contributes to Cocaine Effects on Synapse Structure and Psychostimulant Behavior
Giza JI, Jung Y, Jeffrey RA, Neugebauer NM, Picciotto MR, Biederer T. The Synaptic Adhesion Molecule SynCAM 1 Contributes to Cocaine Effects on Synapse Structure and Psychostimulant Behavior. Neuropsychopharmacology 2012, 38: 628-638. PMID: 23169347, PMCID: PMC3572459, DOI: 10.1038/npp.2012.226.Peer-Reviewed Original ResearchConceptsNucleus accumbensDrugs of abuseSynCAM 1Cocaine effectsSynapse structureMushroom-type spinesExcitatory synapse numberMedium spiny neuronsAddiction-related behaviorsKO miceSpiny neuronsStubby spinesSynapse numberAdhesion molecule proteinsExcitatory synapsesCocaine administrationTrans-synaptic interactionsKnockout micePsychostimulant effectsNAc synapsesStructural remodelingTherapeutic interventionsSynaptic cleftPsychostimulant cocaineSynapse developmentConstitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine
Jung Y, Mulholland PJ, Wiseman SL, Chandler LJ, Picciotto MR. Constitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine. European Journal Of Neuroscience 2012, 37: 1-9. PMID: 23106536, PMCID: PMC3538958, DOI: 10.1111/ejn.12037.Peer-Reviewed Original ResearchConceptsNucleus accumbensCocaine administrationSpine densitySynaptic plasticityMature mushroom-shaped spinesMushroom spine densityDaily cocaine administrationMushroom-shaped spinesChronic cocaine administrationOverall spine densityElevated locomotor activityExperience-dependent remodelingLipophilic dye DiINAc slicesWT miceMushroom spinesKO miceCocaine treatmentDiolistic labelingSynaptic remodelingBrain slicesBrain areasConstitutive knockoutMature spinesLocomotor activityAgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors
Dietrich MO, Bober J, Ferreira JG, Tellez LA, Mineur YS, Souza DO, Gao XB, Picciotto MR, Araújo I, Liu ZW, Horvath TL. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors. Nature Neuroscience 2012, 15: 1108-1110. PMID: 22729177, PMCID: PMC3411867, DOI: 10.1038/nn.3147.Peer-Reviewed Original Research
2011
Reduced locomotor responses to cocaine in ghrelin-deficient mice
Abizaid A, Mineur YS, Roth RH, Elsworth JD, Sleeman MW, Picciotto MR, Horvath TL. Reduced locomotor responses to cocaine in ghrelin-deficient mice. Neuroscience 2011, 192: 500-506. PMID: 21699961, DOI: 10.1016/j.neuroscience.2011.06.001.Peer-Reviewed Original ResearchConceptsGhrelin KO miceWT miceDopamine releaseLocomotor activityBehavioral effectsDopamine metabolite concentrationsGhrelin-deficient miceLocomotor-stimulating effectsDopamine cell activityEffects of cocaineMesolimbic dopaminergic systemWild-type littermatesOrexigenic hormoneChronic injectionsDopamine utilizationDaily injectionsStriatal dopamineMesolimbic systemWT littermatesDopaminergic systemDaily cocaineFood intakeRewarding effectsPsychostimulant effectsLocomotor responseFACS 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
Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference
Neugebauer NM, Henehan RM, Hales CA, Picciotto MR. Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference. Pharmacology Biochemistry And Behavior 2010, 98: 87-93. PMID: 21172385, PMCID: PMC3030658, DOI: 10.1016/j.pbb.2010.12.015.Peer-Reviewed Original ResearchConceptsGal-/- miceAcute nicotine administrationNicotine CPPPlace preferenceNicotine administrationRewarding effectsRole of galaninEffects of nicotineNucleus accumbens shellClass of drugsAmphetamine place preferenceDrugs of abuseGalanin signalingNeuropeptide galaninCPP chamberAlcohol drinkingNicotine rewardSignificant CPPExtracellular signal-related kinaseAccumbens shellGalanin peptideHigh doseSystem activationAlcohol preferenceSignal-related kinaseLocomotion and Self-Administration Induced by Cocaine in 129/OlaHsd Mice Lacking Galanin
Brabant C, Kuschpel AS, Picciotto MR. Locomotion and Self-Administration Induced by Cocaine in 129/OlaHsd Mice Lacking Galanin. Behavioral Neuroscience 2010, 124: 828-838. PMID: 21038934, PMCID: PMC3058554, DOI: 10.1037/a0021221.Peer-Reviewed Original ResearchConceptsGal KO miceCocaine-induced hyperactivityGalanin receptor agonistCocaine-induced hyperlocomotionSpontaneous motor activityGalanin knockout miceEffects of cocaineDrug takersDoses of cocaineDrugs of abuseSelf-administer cocaineGalanin systemReceptor agonistLocomotor effectsKnockout miceGalaninIntravenous cocaineMotor activityFixed ratio scheduleSelf-AdministrationGenetic deletionMiceCocaineDifferent schedulesRatio scheduleMicroRNA knocks down cocaine
Picciotto MR. MicroRNA knocks down cocaine. Nature 2010, 466: 194-195. PMID: 20613832, DOI: 10.1038/466194a.Peer-Reviewed Original Research
2009
The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration
Lavaur J, Mineur YS, Picciotto MR. The membrane cytoskeletal protein adducin is phosphorylated by protein kinase C in D1 neurons of the nucleus accumbens and dorsal striatum following cocaine administration. Journal Of Neurochemistry 2009, 111: 1129-1137. PMID: 19780900, PMCID: PMC2810345, DOI: 10.1111/j.1471-4159.2009.06405.x.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsBenzazepinesBenzophenanthridinesCalmodulin-Binding ProteinsCocaineCorpus StriatumDopamine AntagonistsDopamine Uptake InhibitorsDose-Response Relationship, DrugEnzyme InhibitorsGene Expression RegulationGreen Fluorescent ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPhosphorylationProtein Kinase CRacloprideReceptors, Dopamine D1Time FactorsConceptsProtein kinase CAdducin phosphorylationKinase CActin-binding proteinsFamily of proteinsPhosphorylation of adducinCytoskeletal protein adducinActin dynamicsCytoskeletal rearrangementsPhosphorylation stateCytoskeletal proteinsAdducinF-actinPhosphorylationNeuronal cytoskeletonCellular architectureProteinSynaptic functionMorphological changesCytoskeletonMedium spiny neuronsSpectrinRegimen of cocaineActinRegulation
2008
Effects of galanin on cocaine-mediated conditioned place preference and ERK signaling in mice
Narasimhaiah R, Kamens HM, Picciotto MR. Effects of galanin on cocaine-mediated conditioned place preference and ERK signaling in mice. Psychopharmacology 2008, 204: 95-102. PMID: 19099295, PMCID: PMC2872184, DOI: 10.1007/s00213-008-1438-7.Peer-Reviewed Original ResearchConceptsVentral tegmental areaEffects of galaninNucleus accumbensNeuropeptide galaninPlace preferenceThreshold doseEffects of morphineMesolimbic dopamine systemMesolimbic dopaminergic pathwaySystemic cocaine injectionPlace preference paradigmCocaine-induced activationDrugs of abuseAmphetamine reinforcementWild-type controlsExtracellular signal-regulated kinase (ERK) activityTegmental areaCocaine injectionCocaine responseDopaminergic pathwaysConclusionsThese dataGalaninRewarding effectsDopamine systemDrug reinforcementEffects of the H3 receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions
Brabant C, Alleva L, Grisar T, Quertemont E, Lakaye B, Ohtsu H, Lin JS, Jatlow P, Picciotto MR, Tirelli E. Effects of the H3 receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions. Psychopharmacology 2008, 202: 673-687. PMID: 18843481, DOI: 10.1007/s00213-008-1345-y.Peer-Reviewed Original ResearchConceptsEffects of thioperamideCocaine-induced hyperlocomotionCocaine-induced locomotionLocomotor effectsHistaminergic systemKnockout micePotential drug-drug interactionsContribution of histamineNon-histaminergic neuronsPlasma cocaine concentrationsPotential pharmacokinetic interactionsCocaine-induced hyperactivityCocaine plasma concentrationsDrug-drug interactionsReceptor inverse agonistInverse agonist thioperamideSelective H3 agonistH3 receptor inverse agonistConclusionsThe present resultsH3 autoreceptorsPharmacokinetic interactionsIntraperitoneal injectionAgonist AHistamine releasePharmacokinetic effectsAdministration 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
Prenatal 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 SyndromeDifferential effects of nicotinic antagonists perfused into the nucleus accumbens or the ventral tegmental area on cocaine-induced dopamine release in the nucleus accumbens of mice
Zanetti L, Picciotto MR, Zoli M. Differential effects of nicotinic antagonists perfused into the nucleus accumbens or the ventral tegmental area on cocaine-induced dopamine release in the nucleus accumbens of mice. Psychopharmacology 2006, 190: 189. PMID: 17061109, DOI: 10.1007/s00213-006-0598-6.Peer-Reviewed Original ResearchConceptsIntra-VTA perfusionVentral tegmental areaDA levelsNucleus accumbensCocaine-elicited increasesPerfusate levelsTegmental areaCocaine-induced dopamine releaseNicotinic acetylcholine receptor antagonistMesolimbic DA neuronsDihydro-β-erythroidineAcetylcholine receptor antagonistEffects of cocaineMesolimbic dopamine systemSubtype-specific mannerDA neuronsNAChR antagonistIntracerebral microdialysisNicotinic antagonistsReceptor antagonistNicotinic pathwayLocal perfusionDopamine releaseDopamine systemPerfusionInhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum
Zanetti L, de Kerchove D’Exaerde A, Zanardi A, Changeux JP, Picciotto MR, Zoli M. Inhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum. Psychopharmacology 2006, 187: 181-188. PMID: 16826402, DOI: 10.1007/s00213-006-0419-y.Peer-Reviewed Original ResearchConceptsExtracellular dopamine levelsDevelopment of sensitizationWild-type miceDopamine levelsVentral striatumCocaine-elicited increasesExtracellular DA levelsAdministration of cocaineDihydro-β-erythroidineAbility of cocaineNicotinic acetylcholine receptorsNicotine treatmentDA levelsNicotinic antagonistsRationaleSeveral studiesNeurochemical responsesConclusionsThese dataObjectivesThe current studySpecific antagonistNAChR blockadeAcetylcholine receptorsElicit increasesStriatumMiceSensitization