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 cultures
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
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
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
2005
Neurobiology and Treatment of Anxiety: Signal Transduction and Neural Plasticity
Duman C, Duman R. Neurobiology and Treatment of Anxiety: Signal Transduction and Neural Plasticity. Handbook Of Experimental Pharmacology 2005, 169: 305-334. PMID: 16594263, DOI: 10.1007/3-540-28082-0_11.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAntidepressive AgentsAnxietyFearHumansMemoryNeuronal PlasticitySecond Messenger SystemsSignal TransductionConceptsCAMP response element-binding proteinSignaling pathwaysAdditional signaling pathwaysIntracellular signaling pathwaysResponse element-binding proteinElement-binding proteinTreatment of anxietyNeuronal plasticitySignal transductionAnxiolytic effectivenessChronic antidepressant actionBinding proteinCellular mechanismsChronic antidepressant treatmentFunctional plasticityImportance of mechanismsPathophysiology of anxietyPathwayPlasticityProteinAntidepressant treatmentAntidepressant actionFunctional outcomeMolecular alterationsTreatment strategies