2020
GABA 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 cultures
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 ResearchMeSH KeywordsAnimalsAntidepressive AgentsBehavior, AnimalKetamineMaleMice, Inbred C57BLOligopeptidesPrefrontal CortexRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSynapsesConceptsPsychotomimetic 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
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