2022
ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms
Mineur YS, Mose TN, Maibom KL, Pittenger ST, Soares AR, Wu H, Taylor SR, Huang Y, Picciotto MR. ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms. Molecular Psychiatry 2022, 27: 4918-4927. PMID: 36050437, PMCID: PMC10718266, DOI: 10.1038/s41380-022-01749-7.Peer-Reviewed Original ResearchConceptsBasolateral amygdalaBLA neuronsBalance of inhibitoryHuman mood disordersLight-dark boxGABA interneuronsPV neuronsVIP neuronsCalmodulin-dependent protein kinase IIMale miceACh levelsMood disordersTail suspensionNeuronal activityNeuron subtypesAcetylcholineChronic stressInhibitory signalingBalance of activityHomeostatic functionsBLA activityStress-induced changesNeuronsSocial defeatProtein kinase II
2020
Ronald S. Duman, PhD (1954–2020)
Taylor J, DiLeone R, Picciotto M. Ronald S. Duman, PhD (1954–2020). Nature Neuroscience 2020, 23: 595-595. PMCID: PMC7190563, DOI: 10.1038/s41593-020-0629-3.Commentaries, Editorials and LettersGABA 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
2016
Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex
McClure-Begley TD, Esterlis I, Stone KL, Lam TT, Grady SR, Colangelo CM, Lindstrom JM, Marks MJ, Picciotto MR. Evaluation of the Nicotinic Acetylcholine Receptor-Associated Proteome at Baseline and Following Nicotine Exposure in Human and Mouse Cortex. ENeuro 2016, 3: eneuro.0166-16.2016. PMID: 27559543, PMCID: PMC4985585, DOI: 10.1523/eneuro.0166-16.2016.Peer-Reviewed Original ResearchConceptsPutative interacting proteinsQuantitative proteomic assessmentProtein-protein interactionsTemporal cortex tissueChaperone familyMood disordersInteracting proteinProtein complexesPresynaptic neurotransmitter releaseNovel etiological mechanismsNicotine exposureProteomic assessmentProteomeNicotinic acetylcholine receptorsMouse cortexProteinHigh-affinity nAChRsΒ2 subunitCortex of miceMaintenance of smokingNew treatment targetsResult of smokingNeurotransmitter releaseAcetylcholine receptorsPrimary function
2015
Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states
Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS. Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states. Neuropharmacology 2015, 96: 235-243. PMID: 25582289, PMCID: PMC4486625, DOI: 10.1016/j.neuropharm.2014.12.028.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsNicotinic medicationsAcetylcholine receptorsNicotinic agentsRole of nAChRsEffects of nicotineBehavioral statesSelf-medicate symptomsNicotinic effectsClinical trialsClinical studiesMood disordersPsychiatric disordersAnimal modelsAffective disordersMedicationsTobacco productsAnxiety regulationRelated constructsMental statesReceptorsDisordersNAChRsNicotineMood
2014
Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine
Mineur YS, Einstein EB, Bentham MP, Wigestrand MB, Blakeman S, Newbold SA, Picciotto MR. Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine. Neuropsychopharmacology 2014, 40: 938-946. PMID: 25288485, PMCID: PMC4330507, DOI: 10.1038/npp.2014.269.Peer-Reviewed Original ResearchMeSH Keywords8-Hydroxy-2-(di-n-propylamino)tetralinAlkaloidsAnimalsAntidepressive AgentsAzocinesDisease Models, AnimalDrug SynergismFluoxetineGene Expression RegulationHEK293 CellsHindlimb SuspensionHippocampusHumansInterpersonal RelationsMaleMiceMice, Inbred C57BLMotor ActivityQuinolizinesReceptor, Serotonin, 5-HT1ASelective Serotonin Reuptake InhibitorsSerotonin Receptor AgonistsStress, PsychologicalConceptsAntidepressant-like effectsSelective serotonin reuptake inhibitorsDorsal rapheCholinergic systemAgonist cytisineNicotinic acetylcholine receptor blockersEffects of cytisineTreatment-resistant patientsSerotonin reuptake inhibitorsAcetylcholine receptor blockerSSRI fluoxetineReceptor blockersAntidepressant efficacyReuptake inhibitorsSerotonin depletionCholinergic drugsMood disordersSerotonin receptorsMouse modelPharmacological approachesHippocampusReceptorsCytisineRapheMolecular mechanismsCalcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice
Mineur YS, Taylor SR, Picciotto MR. Calcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice. Biological Psychiatry 2014, 75: 991-998. PMID: 24742621, PMCID: PMC4037359, DOI: 10.1016/j.biopsych.2014.03.009.Peer-Reviewed Original ResearchConceptsDepression-like behaviorOrgan transplant patientsAnxiety-like behaviorTransplant patientsMood disordersCalcineurin activityIncidence of anxietyCalcineurin inhibitor cyclosporine ALight/dark boxPotential clinical consequencesOpen field testSymptoms of anxietyChronic blockadeChronic administrationTransplant rejectionCsA treatmentRole of calcineurinSystemic inhibitionMale miceClinical consequencesCyclosporine ACalcineurin levelsBrain areasCalcium-dependent phosphatase calcineurinGene transfer approach
2013
High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness
Lewis AS, Picciotto MR. High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness. Psychopharmacology 2013, 229: 477-485. PMID: 23624811, PMCID: PMC3766461, DOI: 10.1007/s00213-013-3126-5.Peer-Reviewed Original ResearchConceptsPsychiatric illnessNicotinic acetylcholine receptor expressionPre-clinical animal modelsMultiple psychiatric illnessesChronic nicotine exposureHigh-affinity nAChRsAcetylcholine receptor expressionNicotinic receptor subtypesNovel therapeutic agentsHuman psychiatric illnessCholinergic dysfunctionClinical featuresNicotine exposurePatient populationCholinergic systemNicotine intakeReceptor expressionReceptor subtypesMood disordersTobacco usePharmacological agentsAnimal modelsPsychiatric diseasesAcetylcholine receptorsIllnessCholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior
Mineur YS, Obayemi A, Wigestrand MB, Fote GM, Calarco CA, Li AM, Picciotto MR. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3573-3578. PMID: 23401542, PMCID: PMC3587265, DOI: 10.1073/pnas.1219731110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholinesteraseAnimalsAntidepressive AgentsAnxietyBehavior, AnimalCholinergic AntagonistsCholinergic NeuronsDependovirusDepressionFluoxetineGene Knockdown TechniquesHindlimb SuspensionHippocampusHumansMaleMiceMice, Inbred C57BLPhenotypePhysostigmineReceptors, CholinergicResilience, PsychologicalRNA, Small InterferingSignal TransductionStress, PsychologicalTime FactorsConceptsDepression-like behaviorShRNA-mediated knockdownSelective serotonin reuptake inhibitor fluoxetineSerotonin reuptake inhibitor fluoxetineAChE inhibitor physostigmineAdministration of fluoxetineBlockade of acetylcholinesteraseEndophenotypes of depressionHippocampal AChE activityAntidepressant-like effectsReuptake inhibitor fluoxetineAChE activityDepression-like phenotypeSymptoms of depressionSocial defeat paradigmHippocampal AChEMuscarinic antagonistCholinergic drugsInhibitor physostigmineCholinergic systemClinical trialsSystemic administrationMood disordersSystemic effectsAnimal models
2011
&agr;4&bgr;2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties
Mineur YS, Einstein EB, Seymour PA, Coe JW, O'Neill BT, Rollema H, Picciotto MR. &agr;4&bgr;2 nicotinic acetylcholine receptor partial agonists with low intrinsic efficacy have antidepressant-like properties. Behavioural Pharmacology 2011, 22: 291-299. PMID: 21566524, PMCID: PMC3227135, DOI: 10.1097/fbp.0b013e328347546d.Peer-Reviewed Original ResearchConceptsNovelty-suppressed feeding testPartial agonistNicotinic acetylcholine receptor partial agonistAcceptable side effect profileAntidepressant-like effectsAntidepressant-like propertiesSide effect profileTail suspension testForced-swim testReceptor partial agonistLow intrinsic efficacyNicotinic acetylcholine receptorsAntidepressant efficacyFeeding testsReduced immobilityAntidepressant propertiesMood disordersNicotinic compoundsΑ4β2 nAChRsAcetylcholine receptorsLocomotor activityIntrinsic efficacyFunctional efficacySubtype selectivityTime points
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 subjectsPatientsCytisine-Based Nicotinic Partial Agonists as Novel Antidepressant Compounds
Mineur YS, Eibl C, Young G, Kochevar C, Papke RL, Gündisch D, Picciotto MR. Cytisine-Based Nicotinic Partial Agonists as Novel Antidepressant Compounds. Journal Of Pharmacology And Experimental Therapeutics 2009, 329: 377-386. PMID: 19164465, PMCID: PMC2670591, DOI: 10.1124/jpet.108.149609.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAntidepressive AgentsAzocinesCloning, MolecularData Interpretation, StatisticalElectrophysiologyEnvironmentFeeding BehaviorHindlimb SuspensionLaburnumMaleMiceMice, Inbred C57BLMotor ActivityNicotinic AgonistsOocytesPatch-Clamp TechniquesQuinolizinesReceptors, CholinergicSwimmingXenopus laevisConceptsAntidepressant-like effectsAntidepressant-like propertiesNicotinic partial agonistPartial agonistAntidepressant efficacyDose-dependent antidepressant-like effectNovelty-suppressed feeding testC57/BL6 miceBeta2 nAChRsAntidepressant-like activityTail suspension testBlood-brain barrierSelective partial agonistNicotinic acetylcholine receptorsNovel antidepressantsDevelopment of drugsBL6 miceAlpha3/beta4Alpha7 nAChRsAgonist effectsMood disordersRodent modelsSuspension testTail suspensionMouse model