2024
Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses
Fogaça M, Daher F, Picciotto M. Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses. Neuropsychopharmacology 2024, 1-12. PMID: 39390105, DOI: 10.1038/s41386-024-02002-1.Peer-Reviewed Original ResearchNovelty suppressed feeding testMedial prefrontal cortexSucrose splash testEffects of ketamineAntidepressant-like responseMajor depressive disorderGABAergic activityGABA interneuronsGlutamatergic activityGABA neuronsSustained antidepressant effectsGABA neuron activityLow dose of ketamineAdministration of ketamineDose of ketamineAntidepressant responseAntidepressant developmentSplash testAntidepressant effectsPrefrontal cortexDepressive disorderChemogenetic inhibitionBehavioral actionsAssociated with disruptionGABA function
2023
M1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses
Fogaça M, Wu M, Li C, Li X, Duman R, Picciotto M. M1 acetylcholine receptors in somatostatin interneurons contribute to GABAergic and glutamatergic plasticity in the mPFC and antidepressant-like responses. Neuropsychopharmacology 2023, 48: 1277-1287. PMID: 37142667, PMCID: PMC10354201, DOI: 10.1038/s41386-023-01583-7.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMedial prefrontal cortexGABAergic functionSomatostatin interneuronsSST interneuronsGlutamatergic plasticityAcetylcholine receptorsNon-selective muscarinic receptor antagonistRapid antidepressant-like effectsAntidepressant-like responseImpaired synaptic plasticityChronic unpredictable stressMuscarinic receptor antagonistModulation of excitatoryMajor depressive disorderScopolamine-induced increaseStress-induced impairmentM1 acetylcholine receptorExpression of GABAergicAntidepressant developmentGlutamatergic markersReceptor antagonistDepressive disorderLimbic regionsUnpredictable stress
2021
Sex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders
Peltier MR, Verplaetse TL, Mineur YS, Gueorguieva R, Petrakis I, Cosgrove KP, Picciotto MR, McKee SA. Sex differences in progestogen- and androgen-derived neurosteroids in vulnerability to alcohol and stress-related disorders. Neuropharmacology 2021, 187: 108499. PMID: 33600842, PMCID: PMC7992136, DOI: 10.1016/j.neuropharm.2021.108499.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsStress-related disordersAlcohol useMajor depressive disorderAlcohol-related disordersAlcohol use disorderPosttraumatic stress disorderStress regulation systemComplex comorbiditiesDepressive disorderProblematic alcohol useUse disordersAlcohol misuseTherapeutic potentialTrauma exposureSubstance abuseStress disorderAnxiety disordersDisordersExposure resultsProgestogensNeurosteroidsNegative affectWomenComorbiditiesMale counterparts
2020
Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses
Fogaça MV, Wu M, Li C, Li XY, Picciotto MR, Duman RS. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. Molecular Psychiatry 2020, 26: 3277-3291. PMID: 33070149, PMCID: PMC8052382, DOI: 10.1038/s41380-020-00916-y.Peer-Reviewed Original ResearchConceptsGABA interneuronsRapid antidepressant responseMajor depressive disorderAntidepressant effectsSynaptic plasticityAntidepressant responseRapid-acting antidepressantsAcetylcholine muscarinic receptor antagonistMuscarinic receptor antagonistCortical brain areasEffects of scopolamineAntidepressant actionChemogenetic inhibitionGABAergic interneuronsReceptor antagonistDepressive disorderMale miceInterneuron subtypesBrain areasInterneuronsMPFCTransient inhibitionAffective behaviorInhibitionSubtypesPositive 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 disorder
2016
GABA interneurons mediate the rapid antidepressant-like effects of scopolamine
Wohleb ES, Wu M, Gerhard DM, Taylor SR, Picciotto MR, Alreja M, Duman RS. GABA interneurons mediate the rapid antidepressant-like effects of scopolamine. Journal Of Clinical Investigation 2016, 126: 2482-2494. PMID: 27270172, PMCID: PMC4922686, DOI: 10.1172/jci85033.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMajor depressive disorderMedial prefrontal cortexRapid antidepressant-like effectsRapid antidepressant effectsM1-AChRAntidepressant effectsGABA interneuronsSST interneuronsM1-type muscarinic acetylcholine receptorsNonselective muscarinic acetylcholine receptor antagonistMuscarinic acetylcholine receptor antagonistAcetylcholine receptor antagonistMuscarinic acetylcholine receptorsViral-mediated knockdownPromising pharmacological targetActivity-dependent synapticAntidepressant therapyGABAergic neuronsSomatostatin interneuronsGlutamatergic neuronsSocioeconomic burdenGABAergic interneuronsGlutamatergic interneuronsReceptor antagonist
2015
Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress
Mineur YS, Fote GM, Blakeman S, Cahuzac EL, Newbold SA, Picciotto MR. Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress. Neuropsychopharmacology 2015, 41: 1579-1587. PMID: 26471256, PMCID: PMC4832019, DOI: 10.1038/npp.2015.316.Peer-Reviewed Original ResearchConceptsDepression-like behaviorBasolateral amygdalaΑ7 nAChRsCholinergic signalingMultiple nicotinic acetylcholine receptor subtypesNon-selective nAChR antagonist mecamylamineNicotinic acetylcholine receptor activityNicotinic acetylcholine receptor subtypesStress-mediated behaviorsAntidepressant-like effectsAcetylcholine receptor activityC-Fos immunoreactivityNAChR antagonist mecamylamineAcetylcholine receptor subtypesEffects of nicotineMajor depressive disorderSocial defeat stressAnxiety-like behaviorPre-clinical studiesHuman clinical trialsModels of anxietyMouse behavioral modelsHypercholinergic stateAntagonist mecamylamineLocal infusion
2012
Persistent β2*-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder
Saricicek A, Esterlis I, Maloney KH, Mineur YS, Ruf BM, Muralidharan A, Chen JI, Cosgrove KP, Kerestes R, Ghose S, Tamminga CA, Pittman B, Bois F, Tamagnan G, Seibyl J, Picciotto MR, Staley JK, Bhagwagar Z. Persistent β2*-Nicotinic Acetylcholinergic Receptor Dysfunction in Major Depressive Disorder. American Journal Of Psychiatry 2012, 169: 851-859. PMID: 22772158, PMCID: PMC3494404, DOI: 10.1176/appi.ajp.2012.11101546.Peer-Reviewed Original ResearchConceptsMajor depressive disorderNAChR availabilityDepressed patientsComparison subjectsDepressed subjectsDepressive disorderReceptor availabilityAge-matched comparison subjectsLower receptor availabilityEarly-onset depressionPostmortem brain samplesDopamine receptor availabilityNicotinic acetylcholine receptorsSingle photon emissionPost-mortem samplesEndogenous acetylcholinePrefrontal cortex samplesReceptor dysfunctionDepressive episodePostmortem studiesTrauma ScoreIll subjectsSPECT ligandHealthy subjectsSPECT scans
2010
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis
Mineur YS, Picciotto MR. Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis. Trends In Pharmacological Sciences 2010, 31: 580-586. PMID: 20965579, PMCID: PMC2991594, DOI: 10.1016/j.tips.2010.09.004.Peer-Reviewed Original ResearchConceptsEffects of nicotineDepressive symptomsNeuronal nAChRsNovel antidepressant medicationsDepression-like behaviorMajor depressive disorderNicotinic acetylcholine receptorsAntidepressant medicationNicotine receptorsCholinergic systemDepressive disorderCholinergic hypothesisPreclinical studiesNicotinic drugsPharmacological agentsNicotinic agentsAcetylcholine receptorsEndogenous neurotransmittersSymptomsNAChRsNicotineSmokingDepressed individualsAcetylcholineReceptors
2006
Antidepressant-Like Effects of Ceftriaxone in Male C57BL/6J Mice
Mineur YS, Picciotto MR, Sanacora G. Antidepressant-Like Effects of Ceftriaxone in Male C57BL/6J Mice. Biological Psychiatry 2006, 61: 250-252. PMID: 16860779, DOI: 10.1016/j.biopsych.2006.04.037.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMajor depressive disorderUptake of glutamateBeta-lactam antibiotic agentsNovelty-suppressed feeding testExcessive glutamatergic neurotransmissionDepressive-like behaviorAntidepressant-like activityMale C57BL/6J miceTail suspension testNovelty-suppressed feedingCeftriaxone treatmentC57BL/6J miceGlutamatergic neurotransmissionDepressive disorderAntidepressant compoundsSuspension testMouse modelThree monthsCeftriaxoneAntibiotic agentsRecent evidenceMiceSimilar effectsFeeding tests