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
2015
Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice
Mineur YS, Bentham MP, Zhou WL, Plantenga ME, McKee SA, Picciotto MR. Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice. Psychopharmacology 2015, 232: 3539-3549. PMID: 26146014, PMCID: PMC4561580, DOI: 10.1007/s00213-015-4001-3.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsPaired-pulse ratioC-Fos immunoreactivityPrefrontal cortexSwim testBrain areasRobust antidepressant-like effectsBrain regionsSex differencesMale C57BL/6J miceDepression-like behaviorEffects of guanfacineAcetylcholinesterase inhibitor physostigmineLight/dark boxBaseline sex differencesC-fos expressionDepression-like stateCritical brain regionsDifferent brain areasSex-specific changesAntidepressant efficacyCholinergic controlInhibitor physostigmineC57BL/6J miceAgonist guanfacine
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 mechanisms
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
Cytisine-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
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
2006
The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice
Rabenstein RL, Caldarone BJ, Picciotto MR. The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice. Psychopharmacology 2006, 189: 395-401. PMID: 17016705, DOI: 10.1007/s00213-006-0568-z.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsAntagonist mecamylamineNicotinic acetylcholine receptor activityNoncompetitive nAChR antagonist mecamylamineAntagonist dihydro-β-erythroidineΑ7 knockout miceΑ7-nAChR subunitAcetylcholine receptor activityEffects of mecamylamineNAChR antagonist mecamylamineDihydro-β-erythroidineNicotinic antagonist mecamylamineSubunit knockout miceBaseline locomotor activityDose-response studyMethodsAdult miceAntagonist hexamethoniumAntidepressant efficacyAntidepressant responseCentral nAChRsImmobility timeCholinergic transmissionSwim testMecamylamineSuspension test