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
Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents
Ghosal S, Duman CH, Liu RJ, Wu M, Terwilliger R, Girgenti MJ, Wohleb E, Fogaca MV, Teichman EM, Hare B, Duman RS. Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents. Neurobiology Of Disease 2019, 134: 104669. PMID: 31707118, DOI: 10.1016/j.nbd.2019.104669.Peer-Reviewed Original ResearchConceptsChronic unpredictable stressMedial prefrontal cortexInhibitory post-synaptic currentsGABAergic transmissionSingle doseMale rodentsPrefrontal cortexImbalance of inhibitoryMPFC pyramidal neuronsDepressive-like behaviorDepression-like behaviorStress-induced impairmentModel of depressionPost-synaptic currentsPrecise cellular mechanismsGABAergic proteinsAntidepressant ketamineSynaptic deficitsGABAergic synapsesPyramidal neuronsSynaptic markersGABA markersGlutamate neurotransmissionDepressive behaviorGABA neurotransmissionN-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
2017
Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-like Behavior
Wohleb ES, Terwilliger R, Duman CH, Duman RS. Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-like Behavior. Biological Psychiatry 2017, 83: 38-49. PMID: 28697890, PMCID: PMC6506225, DOI: 10.1016/j.biopsych.2017.05.026.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxietyChronic DiseaseDepressive DisorderDisease Models, AnimalFemaleMacrophage Colony-Stimulating FactorMaleMice, Inbred C57BLMice, TransgenicMicrogliaNeuronal PlasticityNeuronsPhagocytosisPrefrontal CortexReceptor, Macrophage Colony-Stimulating FactorRNA, MessengerSex CharacteristicsStress, PsychologicalUncertaintyConceptsDepressive-like behaviorChronic unpredictable stressMedial prefrontal cortexDendritic spine densityNeuronal remodelingSynaptic deficitsDevelopment of anxietyMessenger RNA levelsPrefrontal cortexSpine densityFemale miceFunctional changesStress exposureNeuron-microglia interactionsRNA levelsChronic stress exposureStress-induced elevationPostmortem dorsolateral prefrontal cortexDorsolateral prefrontal cortexBehavioral consequencesNeuronal atrophyPyramidal neuronsMicroglia functionMale miceUnpredictable stress
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
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