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
2016
GLYX-13 Produces Rapid Antidepressant Responses with Key Synaptic and Behavioral Effects Distinct from Ketamine
Liu RJ, Duman C, Kato T, Hare B, Lopresto D, Bang E, Burgdorf J, Moskal J, Taylor J, Aghajanian G, Duman RS. GLYX-13 Produces Rapid Antidepressant Responses with Key Synaptic and Behavioral Effects Distinct from Ketamine. Neuropsychopharmacology 2016, 42: 1231-1242. PMID: 27634355, PMCID: PMC5437877, DOI: 10.1038/npp.2016.202.Peer-Reviewed Original ResearchConceptsPsychotomimetic side effectsGLYX-13Prefrontal cortexSide effectsGlycine-site partial agonist propertiesLayer V pyramidal neuronsSerial reaction time taskAntidepressant behavioral actionsBehavioral actionsRapid antidepressant effectsRapid acting antidepressantsRapid antidepressant responseApical dendritic tuftsMedial PFCNMDA receptor modulatorsPartial agonist propertiesMedial prefrontal cortexActing antidepressantsAntidepressant actionAntidepressant effectsThalamocortical synapsesAntidepressant responsePyramidal neuronsSingle doseDendritic tufts
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
2010
Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats
Hermes G, Li N, Duman C, Duman R. Post-weaning chronic social isolation produces profound behavioral dysregulation with decreases in prefrontal cortex synaptic-associated protein expression in female rats. Physiology & Behavior 2010, 104: 354-359. PMID: 21185848, PMCID: PMC3387788, DOI: 10.1016/j.physbeh.2010.12.019.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAnimals, NewbornBehavioral SymptomsBody WeightDisks Large Homolog 4 ProteinEstriolEstrusExploratory BehaviorFemaleFood DeprivationGene Expression Regulation, DevelopmentalIntracellular Signaling Peptides and ProteinsMembrane ProteinsPrefrontal CortexPregnancyRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSocial IsolationSynapsinsConceptsFemale ratsNovelty-suppressed feeding testPrefrontal cortexSocial isolationPost-weaning social isolationSynapse-related proteinsChronic social isolationFemale Sprague-DawleyEarly life stressorsSerotonergic functionGlutamate receptorsSprague-DawleyMale rodentsMaternal separationProtein PSD95Profound dysregulationNeuropsychiatric disordersBrain developmentRatsAnxiety disordersMarked deficitDeprivation resultsProtein expressionAdult animalsBiochemical effects
2009
Erythropoietin Induction by Electroconvulsive Seizure, Gene Regulation, and Antidepressant-Like Behavioral Effects
Girgenti MJ, Hunsberger J, Duman CH, Sathyanesan M, Terwilliger R, Newton SS. Erythropoietin Induction by Electroconvulsive Seizure, Gene Regulation, and Antidepressant-Like Behavioral Effects. Biological Psychiatry 2009, 66: 267-274. PMID: 19185286, DOI: 10.1016/j.biopsych.2008.12.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBehavior, AnimalBrain-Derived Neurotrophic FactorDepressionDisease Models, AnimalElectroshockErythropoietinExploratory BehaviorGene Expression ProfilingGene Expression RegulationHumansHypoxia-Inducible Factor 1, alpha SubunitLocomotionMaleOligonucleotide Array Sequence AnalysisRatsRats, Sprague-DawleyReceptors, ErythropoietinSeizuresSwimmingConceptsElectroconvulsive seizuresBehavioral effectsNIH testEPO receptorTrophic effectsRobust antidepressant-like effectsAntidepressant-like behavioral effectsBrain-derived neurotrophic factorAntidepressant-like efficacyTranscription factor hypoxiaAntidepressant-like effectsMultiple brain regionsQuantitative polymerase chain reactionExpression of erythropoietinAntidepressant actionAntidepressant effectsPeripheral administrationNeurotrophic factorIntracerebroventricular infusionPolymerase chain reactionTrophic actionNeurotrophic genesAnimal modelsChoroid plexusRegulation of erythropoietin
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
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