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 proteins
2019
N-Methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects
Fogaça MV, Fukumoto K, Franklin T, Liu RJ, Duman CH, Vitolo OV, Duman RS. N-Methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORC1-dependent antidepressant effects. Neuropsychopharmacology 2019, 44: 2230-2238. PMID: 31454827, PMCID: PMC6898593, DOI: 10.1038/s41386-019-0501-x.Peer-Reviewed Original ResearchConceptsNovelty-suppressed feeding testMedial prefrontal cortexD-methadoneNMDA receptor antagonistAntidepressant actionPhospho-p70S6 kinaseReceptor antagonistN-methyl-D-aspartate receptorsNoncompetitive NMDA receptor antagonistTreatment-resistant patientsChronic unpredictable stressRapid antidepressant actionsDissociative side effectsPrimary cortical culturesMeasures of anhedoniaKetamine inducesAvailable antidepressantsTolerability profileAntidepressant effectsBDNF releaseAntidepressant responseResistant patientsFavorable safetySingle doseCortical culturesSestrin 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
2018
Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine
Fukumoto K, Fogaça M, Liu RJ, Duman C, Kato T, Li XY, Duman RS. Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 116: 297-302. PMID: 30559184, PMCID: PMC6320534, DOI: 10.1073/pnas.1814709116.Peer-Reviewed Original ResearchConceptsActivity-dependent BDNF releaseAntidepressant effectsAntidepressant actionBDNF releaseActivity-dependent brain-derived neurotrophic factorL-type voltage-dependent CaSynaptic functionBrain-derived neurotrophic factorMajor depressive disorder patientsMethyl-d-aspartate (NMDA) receptor antagonistIntra-mPFC microinjectionRapid antidepressant effectsDepressive disorder patientsTreatment of MDDBDNF Val66Met allelesVoltage-dependent CaIntra-mPFC infusionMetabolite of ketamineDownstream TrkBNeurotrophic factorReceptor antagonistNMDA receptorsMolecular signaling mechanismsRodent modelsDisorder patients
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
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
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 relevanceTreatmentFactorsMiceAdministrationBrain