2019
Induction of reversible bidirectional social approach bias by olfactory conditioning in male mice
Chan J, Stout D, Pittenger ST, Picciotto MR, Lewis AS. Induction of reversible bidirectional social approach bias by olfactory conditioning in male mice. Social Neuroscience 2019, 15: 25-35. PMID: 31303111, PMCID: PMC6980898, DOI: 10.1080/17470919.2019.1644370.Peer-Reviewed Original ResearchConceptsPositive social experiencesSocial avoidanceSocial experienceNegative social experiencesBrief social defeatApproach biasNeural representationApproach behaviorExperience valenceBehavioral paradigmsBehavioral confoundsMost paradigmsNegative conditioningOlfactory conditioningSocial approachSocial defeatBrain regionsSubstantial functional impairmentAvoidanceConditioningParadigmNeuropsychiatric disordersFunctional impairmentExperienceConfoundsPerinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice
Lee AM, Picciotto MR. Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice. Behavioural Brain Research 2019, 367: 176-180. PMID: 30959127, PMCID: PMC6481625, DOI: 10.1016/j.bbr.2019.04.007.Peer-Reviewed Original ResearchConceptsNicotine exposureSingle-pellet reaching taskMotor tasksCortical synaptic plasticityPerinatal nicotine exposureDevelopmental nicotine exposureGross motor functionNicotine-treated animalsNicotine-induced changesFemale adult miceSkilled motor taskGross motor performanceAdverse outcomesMotor cortexFemale miceMale miceMotor functionSkilled forelimbPreclinical studiesControl animalsAdult miceImpaired learningSynaptic plasticityFemale pupsMorphologic changesRole of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine
Deyama S, Bang E, Wohleb ES, Li XY, Kato T, Gerhard DM, Dutheil S, Dwyer JM, Taylor SR, Picciotto MR, Duman RS. Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine. American Journal Of Psychiatry 2019, 176: 388-400. PMID: 30606046, PMCID: PMC6494682, DOI: 10.1176/appi.ajp.2018.17121368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingBehavior, AnimalExcitatory Amino Acid AntagonistsGene Knockdown TechniquesGene Knockout TechniquesIn Vitro TechniquesKetamineMiceNeuronsPrefrontal CortexQuinazolinesSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNeuronal vascular endothelial growth factorVascular endothelial growth factorMedial prefrontal cortexRapid antidepressant actionsAntidepressant actionIntra-mPFC infusionSystemic ketamineBehavioral actionsFlk-1Conventional monoamine-based antidepressantsPrefrontal cortexRole of VEGFRapid antidepressant effectsTreatment-resistant depressionMethyl-d-aspartate receptor antagonist ketamineNeuron-specific deletionMonoamine-based antidepressantsNeuron-specific knockoutViral-mediated knockdownEndothelial growth factorVEGF-Flk-1Synaptogenic actionsAntidepressant effectsSynaptogenic effectsLocal knockdown
2017
Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice
Mineur YS, Mose TN, Blakeman S, Picciotto MR. Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice. British Journal Of Pharmacology 2017, 175: 1903-1914. PMID: 28264149, PMCID: PMC5979617, DOI: 10.1111/bph.13769.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBehavior, AnimalDepressionFemaleHippocampusMaleMiceMice, Inbred C57BLPhysostigmineConceptsDepression-like behaviorNicotinic ACh receptorsFemale miceMale miceCholinergic signalingACh receptorsΑ7 nAChRsSignificant antidepressant-like effectΑ7 nicotinic ACh receptorsEffect of α7Antidepressant-like effectsAgonist GTS-21Depression-related behaviorsC-Fos immunoreactivityACh receptor antagonistDepression-like phenotypeAnxiety-like behaviorNicotinic acetylcholine receptorsAnxiety-like phenotypeHippocampal α7Physostigmine administrationAntagonist methyllycaconitineReceptor antagonistSwim testGTS-21
2016
GABA interneurons mediate the rapid antidepressant-like effects of scopolamine
Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, Duman RS. GABA interneurons mediate the rapid antidepressant-like effects of scopolamine. Journal Of Clinical Investigation 2016, 126: 2482-2494. PMID: 27270172, PMCID: PMC4922686, DOI: 10.1172/jci85033.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMajor depressive disorderMedial prefrontal cortexRapid antidepressant-like effectsRapid antidepressant effectsM1-AChRAntidepressant effectsGABA interneuronsSST interneuronsM1-type muscarinic acetylcholine receptorsNonselective muscarinic acetylcholine receptor antagonistMuscarinic acetylcholine receptor antagonistAcetylcholine receptor antagonistMuscarinic acetylcholine receptorsViral-mediated knockdownPromising pharmacological targetActivity-dependent synapticAntidepressant therapyGABAergic neuronsSomatostatin interneuronsGlutamatergic neuronsSocioeconomic burdenGABAergic interneuronsGlutamatergic interneuronsReceptor antagonist
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 exposurePathwayInteractionFilamentsEnrichmentModulation of aggressive behavior in mice by nicotinic receptor subtypes
Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR. Modulation of aggressive behavior in mice by nicotinic receptor subtypes. Biochemical Pharmacology 2015, 97: 488-497. PMID: 26212554, PMCID: PMC4600457, DOI: 10.1016/j.bcp.2015.07.019.Peer-Reviewed Original ResearchConceptsAcute nicotine administrationNicotine administrationHypolocomotor effectNicotinic acetylcholine receptor agonist nicotineAgonist GTS-21Nicotinic receptor subtypesAnti-aggressive propertiesDihydro-β-erythroidineBALB/cNeurobiology of aggressionSocial interaction timeCurrent pharmacotherapyAntagonist methyllycaconitineC57BL/6 miceWorse outcomesGTS-21Receptor subtypesPathological aggressionAgonist nicotineΑ7 nAChRsSpecific treatmentSide effectsPharmacological studiesNeuropsychiatric conditionsNicotine
2014
Calcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice
Mineur YS, Taylor SR, Picciotto MR. Calcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice. Biological Psychiatry 2014, 75: 991-998. PMID: 24742621, PMCID: PMC4037359, DOI: 10.1016/j.biopsych.2014.03.009.Peer-Reviewed Original ResearchConceptsDepression-like behaviorOrgan transplant patientsAnxiety-like behaviorTransplant patientsMood disordersCalcineurin activityIncidence of anxietyCalcineurin inhibitor cyclosporine ALight/dark boxPotential clinical consequencesOpen field testSymptoms of anxietyChronic blockadeChronic administrationTransplant rejectionCsA treatmentRole of calcineurinSystemic inhibitionMale miceClinical consequencesCyclosporine ACalcineurin levelsBrain areasCalcium-dependent phosphatase calcineurinGene transfer approach
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 interneuronsMorphine dependence and withdrawal induced changes in cholinergic signaling
Neugebauer NM, Einstein EB, Lopez MB, McClure-Begley TD, Mineur YS, Picciotto MR. Morphine dependence and withdrawal induced changes in cholinergic signaling. Pharmacology Biochemistry And Behavior 2013, 109: 77-83. PMID: 23651795, PMCID: PMC3690589, DOI: 10.1016/j.pbb.2013.04.015.Peer-Reviewed Original ResearchConceptsMedial habenulaMorphine dependenceCholinergic signalingInterpeduncular nucleusHigh-affinity nicotinic acetylcholine receptorsNicotinic acetylcholine receptor levelsEffects of cholinergicMorphine-dependent miceChronic morphine administrationAcetylcholine receptor levelsC-fos expressionC-Fos activationNicotinic acetylcholine receptorsDependent miceMorphine administrationMorphine withdrawalCholinergic drugsOpiate withdrawalCholinergic systemEpibatidine bindingReceptor levelsSomatic signsNeuronal activityAcetylcholine receptorsNAChR receptorCholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior
Mineur YS, Obayemi A, Wigestrand MB, Fote GM, Calarco CA, Li AM, Picciotto MR. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3573-3578. PMID: 23401542, PMCID: PMC3587265, DOI: 10.1073/pnas.1219731110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholinesteraseAnimalsAntidepressive AgentsAnxietyBehavior, AnimalCholinergic AntagonistsCholinergic NeuronsDependovirusDepressionFluoxetineGene Knockdown TechniquesHindlimb SuspensionHippocampusHumansMaleMiceMice, Inbred C57BLPhenotypePhysostigmineReceptors, CholinergicResilience, PsychologicalRNA, Small InterferingSignal TransductionStress, PsychologicalTime FactorsConceptsDepression-like behaviorShRNA-mediated knockdownSelective serotonin reuptake inhibitor fluoxetineSerotonin reuptake inhibitor fluoxetineAChE inhibitor physostigmineAdministration of fluoxetineBlockade of acetylcholinesteraseEndophenotypes of depressionHippocampal AChE activityAntidepressant-like effectsReuptake inhibitor fluoxetineAChE activityDepression-like phenotypeSymptoms of depressionSocial defeat paradigmHippocampal AChEMuscarinic antagonistCholinergic drugsInhibitor physostigmineCholinergic systemClinical trialsSystemic administrationMood disordersSystemic effectsAnimal models
2012
AgRP 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
Galanin negatively modulates opiate withdrawal via galanin receptor 1
Holmes FE, Armenaki A, Iismaa TP, Einstein EB, Shine J, Picciotto MR, Wynick D, Zachariou V. Galanin negatively modulates opiate withdrawal via galanin receptor 1. Psychopharmacology 2011, 220: 619-625. PMID: 21969124, PMCID: PMC3324978, DOI: 10.1007/s00213-011-2515-x.Peer-Reviewed Original ResearchConceptsGalanin receptor 1Chronic morphine administrationMorphine administrationLocus coeruleusGalanin expressionOpiate withdrawalReceptor 1Distinct G protein-coupled receptorsPrecipitation of withdrawalAction of morphineDoses of morphineWild-type miceTransgenic mouse lineG protein-coupled receptorsExpress galaninGalanin levelsWild-type controlsProtein-coupled receptorsNeuropeptide galaninMorphine dependenceWithdrawal signsOpiate dependenceGalaninTransgenic miceGalR2 geneStriatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory
Venkitaramani DV, Moura PJ, Picciotto MR, Lombroso PJ. Striatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory. European Journal Of Neuroscience 2011, 33: 2288-2298. PMID: 21501258, PMCID: PMC3118976, DOI: 10.1111/j.1460-9568.2011.07687.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalFocal Adhesion Kinase 2HippocampusMemoryMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProtein Tyrosine Phosphatases, Non-ReceptorReceptors, AMPAReceptors, N-Methyl-D-AspartateSynaptic TransmissionConceptsStriatal-enriched protein tyrosine phosphataseSTEP KO miceProtein tyrosine phosphataseBrain-specific phosphataseProline-rich tyrosine kinaseEffect of deletionN-methyl-D-aspartate receptorsERK1/2 substratesNR1/NR2B N‐Methyl‐d‐Aspartate ReceptorsPotential molecular mechanismsTyrosine phosphataseSignaling proteinsTyrosine phosphorylationDownstream effectorsKinase 1/2Molecular mechanismsTyrosine kinaseFunctional importanceKnockout micePhosphorylationSTEP knockout miceSynaptic strengtheningIsoxazole propionic acid (AMPA) receptorsSynaptosomal expressionRegulationDissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380
Caldarone BJ, Wang D, Paterson NE, Manzano M, Fedolak A, Cavino K, Kwan M, Hanania T, Chellappan SK, Kozikowski AP, Olivier B, Picciotto MR, Ghavami A. Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380. Psychopharmacology 2011, 217: 199-210. PMID: 21487659, PMCID: PMC3266849, DOI: 10.1007/s00213-011-2271-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsAzetidinesBehavior, AnimalBenzazepinesBrainData Interpretation, StatisticalDose-Response Relationship, DrugLigandsMaleMiceMice, Inbred BALB CMice, Inbred C57BLMolecular StructureMotor ActivityNicotinic AgonistsProtein BindingPyridinesQuinoxalinesReceptors, NicotinicSwimmingTime FactorsVareniclineConceptsAntidepressant-like effectsAntidepressant-like actionSwim testDuration of actionReceptor occupancyNAChR antagonist mecamylamineDihydro-β-erythroidineAcetylcholine receptor agonistRole of β2Partial agonist vareniclineSymptoms of depressionNAChR β2Antagonist mecamylamineReceptor agonistActive dosesAgonist vareniclineSazetidinePartial agonistVareniclineObjectivesThe studyBehavioral efficacyNAChRsBehavioral responsesAgonistsPromising target
2010
Locomotion 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 scheduleOral nicotine consumption does not affect maternal care or early development in mice but results in modest hyperactivity in adolescence
Heath CJ, Horst NK, Picciotto MR. Oral nicotine consumption does not affect maternal care or early development in mice but results in modest hyperactivity in adolescence. Physiology & Behavior 2010, 101: 764-769. PMID: 20826170, PMCID: PMC2975773, DOI: 10.1016/j.physbeh.2010.08.021.Peer-Reviewed Original ResearchConceptsNicotine administrationMaternal behaviorNeuropharmacological effectsSignificant between-group differencesDrinking water administrationNicotine-exposed micePostnatal weight gainBetween-group differencesOral nicotine consumptionPersistent behavioral alterationsExposure-induced changesNursing miceTransient hyperactivityDrinking waterNicotine exposureEffects of exposureC57BL/6J miceHuman smokingBehavioral alterationsNicotine consumptionPassive nursingWeight gainMiceAdministrationMaternal care
2008
Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus
Rao Y, Lu M, Ge F, Marsh DJ, Qian S, Wang AH, Picciotto MR, Gao XB. Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus. Journal Of Neuroscience 2008, 28: 9101-9110. PMID: 18784290, PMCID: PMC2562258, DOI: 10.1523/jneurosci.1766-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnalysis of VarianceAnimalsAnimals, NewbornBehavior, AnimalBenzazepinesBenzhydryl CompoundsCentral Nervous System StimulantsDopamine AgonistsDose-Response Relationship, DrugExcitatory Amino Acid AgentsGlutamic AcidGreen Fluorescent ProteinsHypothalamic Area, LateralHypothalamic HormonesIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsMelaninsMiceMice, Inbred C57BLMice, TransgenicModafinilMotor ActivityNeuronsNeuropeptidesOrexinsPertussis ToxinPituitary HormonesReceptors, SomatostatinSynapsesSynaptic TransmissionTime FactorsConceptsHypocretin/orexin neuronsMCHR1 KO miceOrexin-containing neuronsLateral hypothalamusWild-type miceOrexin neuronsHypocretin/orexinKO miceMCH receptor 1Action potential firingEffects of modafinilMelanin-Concentrating HormoneHypocretin/orexin signalingGroups of neuronsMCH neuronsMiniature EPSCsWT miceHypocretin/Glutamatergic synapsesOrexin signalingSynaptic transmissionPertussis toxinBrain areasReciprocal innervationInhibitory influenceAdministration 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