Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons
Pothula S, Liu RJ, Wu M, Sliby AN, Picciotto MR, Banerjee P, Duman RS. Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons. Neuropsychopharmacology 2020, 46: 799-808. PMID: 33059355, PMCID: PMC8027594, DOI: 10.1038/s41386-020-00882-7.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMedial prefrontal cortexRapid antidepressant-like effectsGluN2B-containing NMDARsPositive allosteric modulatorsNMDAR positive allosteric modulatorExcitatory neuronsExerts antidepressant-like effectsAntidepressant-like behavioral effectsPrefrontal cortexBehavioral effectsAkt/mTORAntidepressant-like actionChronic unpredictable stressNMDA receptor activityRecent preclinical studiesMajor depressive disorderSpecific knockdownParvalbumin inhibitory neuronsCellular triggersSynaptic proteinsGlutamatergic systemNMDAR activityClinical trialsDepressive disorderCell-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 roles