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 stressPathophysiology of nAChRs: Limbic circuits and related disorders
Mineur Y, Soares A, Etherington I, Abdulla Z, Picciotto M. Pathophysiology of nAChRs: Limbic circuits and related disorders. Pharmacological Research 2023, 191: 106745. PMID: 37011774, DOI: 10.1016/j.phrs.2023.106745.Peer-Reviewed Original ResearchConceptsDepressive disorderMedication developmentLimbic system areasPreclinical pharmacological studiesHuman epidemiological studiesHuman affective disordersNicotinic acetylcholine receptorsAntidepressant efficacyClinical evidenceLimbic circuitsNicotine intakePreclinical modelsSpecific nAChRsEpidemiological studiesCurrent therapeuticsAffective disordersAcetylcholine receptorsRelated disordersPharmacological studiesStress disorderDisordersEtiology of anxietyNAChRsRelevant targetsEfficacy
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
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
2009
Biological Basis for the Co-morbidity Between Smoking and Mood Disorders
Mineur YS, Picciotto MR. Biological Basis for the Co-morbidity Between Smoking and Mood Disorders. Journal Of Dual Diagnosis 2009, 5: 122-130. PMID: 20046987, PMCID: PMC2707026, DOI: 10.1080/15504260902869964.Peer-Reviewed Original ResearchNicotinic antagonistsCholinergic activityDepressed patientsMood disordersNicotinic receptorsNicotine dependenceHigh-affinity nicotinic receptorsChronic nicotine useMajor preventable causeEpisodes of depressionPre-clinical studiesClassical antidepressantsAdjunct therapyPreventable causeDepressive disorderMajor depressionUnderlying biological factorsDepressive symptomsNicotine useSmokingDepressionAntidepressantsDisordersHuman subjectsPatients
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