2023
Pathophysiology 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
2018
Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice
Mineur YS, Cahuzac EL, Mose TN, Bentham MP, Plantenga ME, Thompson DC, Picciotto MR. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology 2018, 43: 2118-2125. PMID: 29472646, PMCID: PMC6098039, DOI: 10.1038/s41386-018-0024-x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdrenergic alpha-AgonistsAlkaloidsAmygdalaAnimalsAnxietyAzocinesCholinesterase InhibitorsDepressionFemaleGene Knockdown TechniquesGuanfacineMaleMiceMice, Inbred C57BLNicotinic AgonistsNorepinephrineParasympathetic Nervous SystemQuinolizinesReceptors, Adrenergic, alpha-2Signal TransductionSympathetic Nervous SystemConceptsAntidepressant-like effectsNoradrenergic systemMale C57BL/6J miceDepression-related behaviorsDepression-like phenotypeNicotinic acetylcholine receptorsAntidepressant efficacyCholinergic interactionsNE terminalsC57BL/6J miceShRNA-mediated knockdownAgonist guanfacineAgonist cytisineClinical studiesSmoking relapseΑ2A receptorsAcute abstinenceBrain areasAcetylcholine receptorsAcetylcholineGuanfacineAmygdalaBehavioral effectsAnxiety disordersStress pathways
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
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
Neuromodulation by acetylcholine: examples from schizophrenia and depression
Higley MJ, Picciotto MR. Neuromodulation by acetylcholine: examples from schizophrenia and depression. Current Opinion In Neurobiology 2014, 29: 88-95. PMID: 24983212, PMCID: PMC4268065, DOI: 10.1016/j.conb.2014.06.004.Peer-Reviewed Original ResearchCalcineurin 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
Cholinergic 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
2008
Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice
Caldarone BJ, King SL, Picciotto MR. Sex differences in anxiety-like behavior and locomotor activity following chronic nicotine exposure in mice. Neuroscience Letters 2008, 439: 187-191. PMID: 18524488, PMCID: PMC2491450, DOI: 10.1016/j.neulet.2008.05.023.Peer-Reviewed Original ResearchConceptsAnxiogenic-like responseChronic nicotineAnxiety-like behaviorLocomotor activationFemale miceLocomotor activityPsychostimulant propertiesChronic nicotine exposureFemale C57BL/6J miceSymptoms of anxietyNicotine variesNicotine exposureOverall incidenceC57BL/6J miceMale miceWildtype miceNicotine intakeNicotinic receptorsOpen armsHigh doseMiceNicotineAnxiety disordersBeta2 subunitBehavioral sensitivity
2007
Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice
Mineur YS, Somenzi O, Picciotto MR. Cytisine, a partial agonist of high-affinity nicotinic acetylcholine receptors, has antidepressant-like properties in male C57BL/6J mice. Neuropharmacology 2007, 52: 1256-1262. PMID: 17320916, PMCID: PMC1959230, DOI: 10.1016/j.neuropharm.2007.01.006.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsAntidepressant-like propertiesAntidepressant efficacyNicotinic acetylcholine receptorsPartial agonistBasolateral amygdalaAcetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsC-Fos immunoreactivityNovel antidepressant drugsC-fos expressionPotential neurobiological correlatesAlpha3/Classical antidepressantsAntidepressant drugsRodent modelsImmunohistochemical analysisNeuronal activityAnimal modelsFull agonistAgonistsNeuronal systemsEfficacyNeurobiological correlatesCytisine
2002
Effect of nicotine and nicotinic receptors on anxiety and depression
Picciotto MR, Brunzell DH, Caldarone BJ. Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport 2002, 13: 1097-1106. PMID: 12151749, DOI: 10.1097/00001756-200207020-00006.Peer-Reviewed Original ResearchConceptsNicotine treatmentActivation of nAChRsDorsal raphe nucleusEffects of nicotineMesolimbic dopamine systemNicotinic acetylcholine receptorsNicotine administrationMonoaminergic transmissionChronic useRaphe nucleusAnxiolytic actionLateral septumNicotinic receptorsClassical neurotransmittersNormal brainAnimal studiesDopamine systemBrain areasAcetylcholine receptorsNicotineEnsemble of studiesNAChRsAnxiety modelsAdministration studiesDepression
2001
Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications
Picciotto M, Caldarone B, Brunzell D, Zachariou V, Stevens T, King S. Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications. Pharmacology & Therapeutics 2001, 92: 89-108. PMID: 11916531, DOI: 10.1016/s0163-7258(01)00161-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSignal transduction pathwaysHomologous recombinationTransduction pathwaysGenetic manipulationMolecular basisBehavioral phenotypesInactivation of nAChRsNicotinic acetylcholine receptorsSubunit compositionSubunitsNeuronal nicotinic receptorsPersistent activationNeurotransmitter releaseRelevant mutationsModel systemPossible clinical implicationsPhysiological propertiesAcetylcholine receptorsPhenotypeAutonomic gangliaNicotinic receptorsDisease statesDrug developmentPharmacological actionsNAChRs