2020
Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT1A receptor stimulation
Fukumoto K, Fogaça M, Liu RJ, Duman CH, Li XY, Chaki S, Duman RS. Medial PFC AMPA receptor and BDNF signaling are required for the rapid and sustained antidepressant-like effects of 5-HT1A receptor stimulation. Neuropsychopharmacology 2020, 45: 1725-1734. PMID: 32396921, PMCID: PMC7419563, DOI: 10.1038/s41386-020-0705-0.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorAntidepressant-like effectsMajor depressive disorderMedial prefrontal cortexMPFC infusionSelective stimulationReceptor antagonistAMPA receptorsNon-competitive N-methyl-D-aspartate (NMDA) receptor antagonistTreatment of MDDN-methyl-D-aspartate receptor antagonistSynaptic functionAntidepressant-like actionNovelty-suppressed feedingAMPA receptor antagonistGlutamate AMPA receptorsMPFC 5Antidepressant effectsNeurotrophic factorReceptor agonistDepressive disorderSerotonergic systemReceptor stimulationReceptor activationSynaptic proteinsGABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions
Gerhard DM, Pothula S, Liu RJ, Wu M, Li XY, Girgenti MJ, Taylor SR, Duman CH, Delpire E, Picciotto M, Wohleb ES, Duman RS. GABA interneurons are the cellular trigger for ketamine’s rapid antidepressant actions. Journal Of Clinical Investigation 2020, 130: 1336-1349. PMID: 31743111, PMCID: PMC7269589, DOI: 10.1172/jci130808.Peer-Reviewed Original ResearchConceptsRapid antidepressant actionsAntidepressant actionGABA interneuronsMedial prefrontal cortexCell-specific knockdownPrinciple neuronsPrefrontal cortexDeletion of GluN2BSingle subanesthetic doseBehavioral actionsAction of ketamineNMDA receptor antagonistExcitatory postsynaptic currentsCellular triggersMajor unmet needKetamine's rapid antidepressant actionsGABA subtypeGluN2B-NMDARsSST interneuronsPostsynaptic currentsReceptor antagonistDepressed patientsSubanesthetic doseExtracellular glutamateMood disorders
2019
Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation
Kato T, Pothula S, Liu RJ, Duman CH, Terwilliger R, Vlasuk GP, Saiah E, Hahm S, Duman RS. Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation. Journal Of Clinical Investigation 2019, 129: 2542-2554. PMID: 30990795, PMCID: PMC6546461, DOI: 10.1172/jci126859.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexRapid acting antidepressantsActing antidepressantsAntidepressant actionAntidepressant effectsBDNF releaseActivity-dependent BDNF releaseRapid antidepressant effectsBlood-brain barrierChronic stress exposureSynaptic deficitsBDNF polymorphismSingle doseBrain barrierSynapse numberPreclinical studiesPharmacological modulationNeuronal activityChronic stressPrefrontal cortexRapid synapticStress exposureBehavioral responsesAmino acid leucineAntidepressants
2014
REDD1 is essential for stress-induced synaptic loss and depressive behavior
Ota KT, Liu RJ, Voleti B, Maldonado-Aviles JG, Duric V, Iwata M, Dutheil S, Duman C, Boikess S, Lewis DA, Stockmeier CA, DiLeone RJ, Rex C, Aghajanian GK, Duman RS. REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nature Medicine 2014, 20: 531-535. PMID: 24728411, PMCID: PMC4016190, DOI: 10.1038/nm.3513.Peer-Reviewed Original Research
2013
Evaluating Effects of EPO in Rodent Behavioral Assays Related to Depression
Duman C, Newton S. Evaluating Effects of EPO in Rodent Behavioral Assays Related to Depression. Methods In Molecular Biology 2013, 982: 127-140. PMID: 23456866, DOI: 10.1007/978-1-62703-308-4_8.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsForced-swim testNeurotrophic actionsNovel object recognition testPotential antidepressant propertiesTreatment of depressionTissue-protective propertiesObject recognition testPotential therapeutic utilityEffect of erythropoietinRodent behavioral modelsAntidepressant propertiesDepressive disorderRodent modelsTherapeutic utilityRodent behavioral assaysNeurotrophic compoundsHyponeophagia testErythropoietinCytokine erythropoietinDepressionImportant regulatorBehavioral assaysProtective propertiesRecognition testAntidepressants
2008
Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise
Duman CH, Schlesinger L, Terwilliger R, Russell DS, Newton SS, Duman RS. Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise. Behavioural Brain Research 2008, 198: 366-371. PMID: 19056428, PMCID: PMC2729431, DOI: 10.1016/j.bbr.2008.11.016.Peer-Reviewed Original ResearchConceptsInsulin-like growth factorAntidepressant-like behaviorForced-swim testGrowth factorChronic IGF-I treatmentNovelty-induced hypophagia testIGF-I administrationEffects of exerciseIGF-I treatmentAntidepressant effectsHypophagia testNeurotrophic factorNeurotrophic mechanismsStress exposureDepressionFunctional relevanceTreatmentFactorsMiceAdministrationBrainVoluntary exercise produces antidepressant and anxiolytic behavioral effects in mice
Duman CH, Schlesinger L, Russell DS, Duman RS. Voluntary exercise produces antidepressant and anxiolytic behavioral effects in mice. Brain Research 2008, 1199: 148-158. PMID: 18267317, PMCID: PMC2330082, DOI: 10.1016/j.brainres.2007.12.047.Peer-Reviewed Original ResearchMeSH KeywordsAmitriptylineAnalysis of VarianceAnimalsAntidepressive Agents, TricyclicAnxietyBehavior, AnimalBrain-Derived Neurotrophic FactorDepressionDisease Models, AnimalEscape ReactionHelplessness, LearnedMaleMaze LearningMiceMice, Inbred C57BLMice, KnockoutMotor ActivityPain MeasurementPhysical Conditioning, AnimalReaction TimeSwimmingTime FactorsConceptsBrain-derived neurotrophic factorAntidepressant-like behavioral responsesAntidepressant-like behavioral changesHeterozygous BDNF knockout miceBDNF knockout miceAntidepressant drug treatmentAntidepressant-like behaviorWheel-running exerciseDrug-treated animalsWild-type miceAnxiolytic behavioral effectsFST performanceSedentary control miceBDNF mRNASubchronic administrationChronic exerciseControl miceNeurotrophic factorBasic research studiesBehavioral responsesVoluntary exerciseBDNF geneDrug treatmentKnockout miceLocomotor activity
2007
Antidepressant actions of the exercise-regulated gene VGF
Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR, Duman RS. Antidepressant actions of the exercise-regulated gene VGF. Nature Medicine 2007, 13: 1476-1482. PMID: 18059283, DOI: 10.1038/nm1669.Peer-Reviewed Original ResearchConceptsAntidepressant actionAntidepressant responseRobust antidepressant responseAction of antidepressantsAntidepressant drug developmentVGF nerve growth factorVGF-derived peptidesPotential therapeutic targetDepressed human subjectsNerve growth factorGrowth factor pathwaysNeurotrophic factorMouse hippocampusTherapeutic targetSynaptic plasticityBrain regionsFactor pathwayGrowth factorTarget genesCustom microarrayHealth benefitsPathway analysisVGFHuman subjectsDrug development
2006
A Role for MAP Kinase Signaling in Behavioral Models of Depression and Antidepressant Treatment
Duman CH, Schlesinger L, Kodama M, Russell DS, Duman RS. A Role for MAP Kinase Signaling in Behavioral Models of Depression and Antidepressant Treatment. Biological Psychiatry 2006, 61: 661-670. PMID: 16945347, DOI: 10.1016/j.biopsych.2006.05.047.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAniline CompoundsAnimalsAntidepressive AgentsBehavior, AnimalBenzamidesBrain-Derived Neurotrophic FactorDepressionDisease Models, AnimalDose-Response Relationship, DrugDrug InteractionsEnzyme InhibitorsHelplessness, LearnedHindlimb SuspensionMaleMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase KinasesMotor ActivitySignal TransductionSwimmingConceptsBrain-derived neurotrophic factorAntidepressant-like effectsAntidepressant treatmentSwim testBDNF heterozygous knockout miceDepressive-like behaviorDepressive-like phenotypeTail suspension testEffects of desipramineHeterozygous knockout miceDepressive behavioral phenotypeEffect of inhibitionRodent behavioral modelsMouse behavioral modelsHeterozygous gene deletionAntidepressant mechanismAcute administrationAcute blockadeNeurotrophic factorAntidepressant drugsSuspension testDepressive phenotypeKnockout miceMEK inhibitionMEK inhibitorsTNFα Signaling in Depression and Anxiety: Behavioral Consequences of Individual Receptor Targeting
Simen BB, Duman CH, Simen AA, Duman RS. TNFα Signaling in Depression and Anxiety: Behavioral Consequences of Individual Receptor Targeting. Biological Psychiatry 2006, 59: 775-785. PMID: 16458261, DOI: 10.1016/j.biopsych.2005.10.013.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsAnxietyBehavior, AnimalConditioning, PsychologicalDepressionDisease Models, AnimalDrinking BehaviorExploratory BehaviorFearGene ExpressionMaze LearningMiceMice, Inbred C57BLMice, KnockoutMotor ActivityReaction TimeReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionSucroseSwimmingTumor Necrosis Factor Decoy ReceptorsTumor Necrosis Factor-alphaConceptsPro-inflammatory cytokinesAntidepressant-like responseDepression-like behaviorDepression-like symptomsDeletion of TNFR1Acute injectionSerum levelsSwim testDepressed patientsMajor depressionReceptor subtypesSickness behaviorWildtype littermatesDepressive symptomsDrinking testPsychiatric conditionsCytokinesReceptor targetingSymptomsFear conditioningPatientsTNFalphaExploratory behaviorMiceBehavioral consequences
2003
Inducible, brain region-specific expression of a dominant negative mutant of c-Jun in transgenic mice decreases sensitivity to cocaine
Peakman M, Colby C, Perrotti L, Tekumalla P, Carle T, Ulery P, Chao J, Duman C, Steffen C, Monteggia L, Allen M, Stock J, Duman R, McNeish J, Barrot M, Self D, Nestler E, Schaeffer E. Inducible, brain region-specific expression of a dominant negative mutant of c-Jun in transgenic mice decreases sensitivity to cocaine. Brain Research 2003, 970: 73-86. PMID: 12706249, DOI: 10.1016/s0006-8993(03)02230-3.Peer-Reviewed Original ResearchConceptsNucleus accumbensFos proteinAdult miceRewarding effectsTransgenic miceBrain regionsBrain region-specific expressionCocaine-induced locomotor activityTranscription factor nuclear factor-kappaBRegion-specific expressionAdministration of cocaineChronic drug administrationGlutamate receptor subunit GluR2Chronic cocaine administrationNuclear factor-kappaBProtein kinase Cdk5C-JunAP-1-mediated transcriptionCocaine administrationFos responsePlace preferenceSubunit GluR2Drug AdministrationFactor-kappaBLocomotor activity
2000
Fear conditioning and latent inhibition in mice lacking the high affinity subclass of nicotinic acetylcholine receptors in the brain
Caldarone B, Duman C, Picciotto M. Fear conditioning and latent inhibition in mice lacking the high affinity subclass of nicotinic acetylcholine receptors in the brain. Neuropharmacology 2000, 39: 2779-2784. PMID: 11044747, DOI: 10.1016/s0028-3908(00)00137-4.Peer-Reviewed Original ResearchConceptsLatent inhibitionFear conditioningLatent inhibition taskTests of cognitionSpecific nicotinic receptor subtypesSpatial learning deficitsCognitive tasksInhibition taskHigh affinity subclassCognitive effectsBehavioral freezingLearning deficitsConditioningFearNicotinic receptor subtypesTaskOverall levelCognitionToneNicotineDeficitsSimilar levelsNicotinic receptorsNicotinic acetylcholine receptorsPrevious studies