2023
Placebo’s role in the rapid antidepressant effect
Sanacora G, Colloca L. Placebo’s role in the rapid antidepressant effect. Nature Mental Health 2023, 1: 820-821. DOI: 10.1038/s44220-023-00141-w.Peer-Reviewed Original ResearchRandomized placebo-controlled studyPlacebo-controlled studyRapid antidepressant effectsRapid antidepressant responseRapid antidepressant actionsStudy arm assignmentAntidepressant actionAntidepressant effectsAntidepressant responseSurgical anesthesiaTreatment assignmentHigh ratePlaceboAnesthesiaKetamineKetamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms
Krystal J, Kavalali E, Monteggia L. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacology 2023, 49: 41-50. PMID: 37488280, PMCID: PMC10700627, DOI: 10.1038/s41386-023-01629-w.Peer-Reviewed Original ResearchConceptsMood disordersEffective treatmentN-methyl-D-aspartate receptorsGlutamatergic N-methyl-D-aspartate receptorRapid antidepressant effectsTreatment-resistant depressionKey clinical aspectsRapid antidepressant actionsNovel effective treatmentsSynaptic signaling mechanismsMore effective treatmentsSynaptic plasticity mechanismsOpen channel blockerAntidepressant actionAntidepressant effectsKetamine effectsChannel blockersClinical aspectsClinical practiceNew treatmentsNeuropsychiatric disordersCircuit mechanismsDisordersTreatmentKetamine
2022
Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine
Saland SK, Wilczak K, Voss E, Lam TT, Kabbaj M. Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine. Scientific Reports 2022, 12: 1820. PMID: 35110693, PMCID: PMC8810966, DOI: 10.1038/s41598-022-05937-x.Peer-Reviewed Original ResearchConceptsLow-dose ketamineFemale ratsMale ratsTherapeutic effectIntact adult male ratsNMDA receptor antagonist ketamineAcute low doseKetamine's therapeutic effectsRapid antidepressant actionsAdult male ratsKetamine-induced changesRapid actionAntidepressant actionAntidepressant ketamineHormonal milieuHormone-dependent modulationHormonal statusLow doseKetamineBrain regionsRatsSynaptic signalingPathway activationBi-directional effectsCritical modulator
2020
Cell-type specific modulation of NMDA receptors triggers antidepressant actions
Pothula S, Kato T, Liu RJ, Wu M, Gerhard D, Shinohara R, Sliby AN, Chowdhury GMI, Behar KL, Sanacora G, Banerjee P, Duman RS. Cell-type specific modulation of NMDA receptors triggers antidepressant actions. Molecular Psychiatry 2020, 26: 5097-5111. PMID: 32488125, DOI: 10.1038/s41380-020-0796-3.Peer-Reviewed Original ResearchConceptsPositive allosteric modulatorsNMDAR positive allosteric modulatorMedial prefrontal cortexAntidepressant effectsAntidepressant actionGlutamate effluxReceptor positive allosteric modulatorPrincipal glutamatergic neuronsAction of ketamineAntidepressant-like effectsRapid antidepressant effectsRapid antidepressant actionsSimilar antidepressant effectsSpecific knockdownCell type-specific modulationCellular triggersGABA interneuronsGlutamate releaseGlutamatergic neuronsPyramidal neuronsNMDAR antagonistsNMDAR activityNMDAR functionExcitatory synapsesCell type-specific rolesGABA 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
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 culturesOptogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
Hare BD, Shinohara R, Liu RJ, Pothula S, DiLeone RJ, Duman RS. Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects. Nature Communications 2019, 10: 223. PMID: 30644390, PMCID: PMC6333924, DOI: 10.1038/s41467-018-08168-9.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAntidepressant effectsPyramidal cellsNovel rapid-acting antidepressantsRapid antidepressant effectsRapid-acting antidepressantsRapid antidepressant responseRapid antidepressant actionsAntidepressant actionAntidepressant responsePyramidal neuronsTherapeutic responseDRD2 dopamine receptorAnxiolytic responseDopamine receptorsSomatic stimulationTarget neuronsImpaired functionMajor subtypesOptogenetic stimulationParticular subtypeDownstream circuitryPrefrontal cortexKetamineNeuronsRole of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine
Deyama S, Bang E, Wohleb ES, Li XY, Kato T, Gerhard DM, Dutheil S, Dwyer JM, Taylor SR, Picciotto MR, Duman RS. Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine. American Journal Of Psychiatry 2019, 176: 388-400. PMID: 30606046, PMCID: PMC6494682, DOI: 10.1176/appi.ajp.2018.17121368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingBehavior, AnimalExcitatory Amino Acid AntagonistsGene Knockdown TechniquesGene Knockout TechniquesIn Vitro TechniquesKetamineMiceNeuronsPrefrontal CortexQuinazolinesSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNeuronal vascular endothelial growth factorVascular endothelial growth factorMedial prefrontal cortexRapid antidepressant actionsAntidepressant actionIntra-mPFC infusionSystemic ketamineBehavioral actionsFlk-1Conventional monoamine-based antidepressantsPrefrontal cortexRole of VEGFRapid antidepressant effectsTreatment-resistant depressionMethyl-d-aspartate receptor antagonist ketamineNeuron-specific deletionMonoamine-based antidepressantsNeuron-specific knockoutViral-mediated knockdownEndothelial growth factorVEGF-Flk-1Synaptogenic actionsAntidepressant effectsSynaptogenic effectsLocal knockdown
2018
Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy
Jiang C, Lin WJ, Salton SR. Role of a VGF/BDNF/TrkB Autoregulatory Feedback Loop in Rapid-Acting Antidepressant Efficacy. Journal Of Molecular Neuroscience 2018, 68: 504-509. PMID: 30022437, PMCID: PMC6338529, DOI: 10.1007/s12031-018-1124-0.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factorRapid-acting antidepressantsTLQP-62Antidepressant efficacyReceptor activationN-methyl-D-aspartate receptorsParticular brain-derived neurotrophic factorIsoxazolepropionic acid receptor (AMPAR) activationBDNF/TrkBDepression-like behaviorRapid antidepressant actionsIntra-hippocampal administrationAMPA receptor activationExpression of VGFChemical antidepressantsAntidepressant actionBDNF expressionSustained efficacyNeurotrophic factorNeurotrophin familySwim testVoluntary exerciseMTOR pathwayMTOR activationAntidepressants
2017
BDNF release and signaling are required for the antidepressant actions of GLYX-13
Kato T, Fogaça MV, Deyama S, Li XY, Fukumoto K, Duman RS. BDNF release and signaling are required for the antidepressant actions of GLYX-13. Molecular Psychiatry 2017, 23: 2007-2017. PMID: 29203848, PMCID: PMC5988860, DOI: 10.1038/mp.2017.220.Peer-Reviewed Original ResearchConceptsGLYX-13Antidepressant actionAntidepressant effectsIntra-medial prefrontal cortex infusionN-methyl-d-aspartate modulatorsActivation of VDCCsAntidepressant behavioral actionsConventional antidepressant medicationRapid antidepressant actionsActivity-dependent releaseVoltage-dependent Ca2Partial agonist propertiesPreclinical rodent modelsBDNF Val66Met allelesBDNF-TrkBAntidepressant medicationBDNF releaseGlutamatergic compoundsMonoaminergic systemsDepressed patientsRodent modelsAgonist propertiesVal66Met alleleTherapeutic efficacyMutant mice
2016
Ketamine’s Mechanism of Rapid Antidepressant Activity: Evidence Gleaned from Clinical Studies
Averill L, Murrough J, Abdallah C. Ketamine’s Mechanism of Rapid Antidepressant Activity: Evidence Gleaned from Clinical Studies. 2016, 99-121. DOI: 10.1007/978-3-319-42925-0_7.Peer-Reviewed Original ResearchRapid antidepressant effectsNeurobiology of depressionRapid antidepressant actionsNovel drug developmentDrug developmentKetamine's rapid antidepressant effectsRapid antidepressant activityOpen-label trialAntidepressant drug developmentKetamine's rapid antidepressant actionsTrauma-related disordersAntidepressant actionAntidepressant effectsAntidepressant medicationKetamine's mechanismSafety profileKetamine responseAntidepressant activityClinical studiesPotential biomarkersPsychotherapeutic treatmentHuman subjectsMedical SciencesDepressionNeurobiologyTransiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects
Chowdhury GM, Zhang J, Thomas M, Banasr M, Ma X, Pittman B, Bristow L, Schaeffer E, Duman RS, Rothman DL, Behar KL, Sanacora G. Transiently increased glutamate cycling in rat PFC is associated with rapid onset of antidepressant-like effects. Molecular Psychiatry 2016, 22: 120-126. PMID: 27067013, PMCID: PMC5345902, DOI: 10.1038/mp.2016.34.Peer-Reviewed Original ResearchConceptsAntidepressant-like efficacyAntidepressant actionRo 25Glutamate cyclingAntidepressant-like effectsRapid antidepressant effectsClear dose-dependent effectRapid antidepressant actionsDose-dependent effectEffects of scopolamineRapid transient riseAntidepressant effectsAntidepressant propertiesIntravenous infusionSingle doseAntidepressant activityIntraperitoneal injectionClinical trialsDrug injectionAwake ratsNovel agentsRat PFCRodent modelsRapid onsetUnique drug
2011
Glutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure
Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS. Glutamate N-methyl-D-aspartate Receptor Antagonists Rapidly Reverse Behavioral and Synaptic Deficits Caused by Chronic Stress Exposure. Biological Psychiatry 2011, 69: 754-761. PMID: 21292242, PMCID: PMC3068225, DOI: 10.1016/j.biopsych.2010.12.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternChoice BehaviorDendritic SpinesElectrophysiologyExcitatory Amino Acid AntagonistsKetamineNeuronsPhenolsPiperidinesPrefrontal CortexRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSignal TransductionSirolimusStress, PhysiologicalStress, PsychologicalSynapsesSynaptic TransmissionConceptsGlutamate N-methyl-d-aspartate (NMDA) receptor antagonistN-methyl-D-aspartate receptor antagonistNMDA receptor antagonistReceptor antagonistLayer V pyramidal neuronsChronic unpredictable stress modelMammalian targetStress exposureDepressant-like behaviorLong-term stress exposurePathophysiology of depressionRapid antidepressant actionsSelective NMDA receptorChronic stress exposurePrefrontal cortex neuronsAntidepressant actionAcute treatmentChronic administrationSynaptic deficitsPyramidal neuronsSpine densityRo 25Cortex neuronsFunctional deficitsNMDA receptors
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