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
2013
Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 12078-12083. PMID: 23818597, PMCID: PMC3718126, DOI: 10.1073/pnas.1307849110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnalysis of VarianceAnimalsBridged Bicyclo Compounds, HeterocyclicCholinergic AgonistsCholinergic AntagonistsCognitionFemaleIontophoresisMacaca mulattaMaleMecamylamineMicroscopy, ImmunoelectronN-MethylaspartatePhenolsPiperidinesPrefrontal CortexQuinuclidinesReceptors, NicotinicSpatial BehaviorSynapsesVisual PerceptionConceptsDorsolateral prefrontal cortexΑ7 nAChRsPrefrontal cortexΑ7 nicotinic acetylcholine receptorGlutamatergic NMDA receptorsCognitive circuitsNicotinic α7 receptorsPrimary visual cortexNMDA receptor actionGenetic insultsNicotinic acetylcholine receptorsDlPFC circuitsPrimate dlPFCACh depletionNMDA actionNMDA receptorsPyramidal cellsΑ7 receptorsNeuronal firingNAChR blockadeAcetylcholine receptorsVisual cortexPersistent firingCognitive functionLow-dose stimulation
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 testInhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum
Zanetti L, de Kerchove D’Exaerde A, Zanardi A, Changeux JP, Picciotto MR, Zoli M. Inhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum. Psychopharmacology 2006, 187: 181-188. PMID: 16826402, DOI: 10.1007/s00213-006-0419-y.Peer-Reviewed Original ResearchConceptsExtracellular dopamine levelsDevelopment of sensitizationWild-type miceDopamine levelsVentral striatumCocaine-elicited increasesExtracellular DA levelsAdministration of cocaineDihydro-β-erythroidineAbility of cocaineNicotinic acetylcholine receptorsNicotine treatmentDA levelsNicotinic antagonistsRationaleSeveral studiesNeurochemical responsesConclusionsThese dataObjectivesThe current studySpecific antagonistNAChR blockadeAcetylcholine receptorsElicit increasesStriatumMiceSensitization
2004
High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation
Caldarone BJ, Harrist A, Cleary MA, Beech RD, King SL, Picciotto MR. High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation. Biological Psychiatry 2004, 56: 657-664. PMID: 15522249, DOI: 10.1016/j.biopsych.2004.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAmitriptylineAnalysis of VarianceAnimalsAntidepressive Agents, TricyclicBehavior, AnimalBromodeoxyuridineCell CountCell ProliferationDose-Response Relationship, DrugDrosophila ProteinsDrug InteractionsHelplessness, LearnedHindlimb SuspensionHippocampusImmunohistochemistryMecamylamineMiceMice, Inbred C57BLMice, KnockoutNeuronsNicotinic AntagonistsNortriptylineReceptors, NicotinicSwimmingConceptsHigh-affinity nAChRsHippocampal cell proliferationNicotinic acetylcholine receptorsSwim testAcetylcholine receptorsCell proliferationHigh-affinity nicotinic acetylcholine receptorsNoncompetitive nAChR antagonist mecamylamineAntagonism of nAChRsAntidepressant-induced increasesAntidepressant-like effectsNAChR antagonist mecamylamineWild-type miceInhibition of nAChRsAntidepressants actAntidepressant actionAntidepressant effectsChronic treatmentAntagonist mecamylamineAntidepressant propertiesTricyclic antidepressantsAntidepressant activityTherapeutic effectKnockout miceNoncompetitive antagonist
2000
Nicotinic modulation of mesoprefrontal dopamine neurons: pharmacologic and neuroanatomic characterization.
George TP, Verrico CD, Picciotto MR, Roth RH. Nicotinic modulation of mesoprefrontal dopamine neurons: pharmacologic and neuroanatomic characterization. Journal Of Pharmacology And Experimental Therapeutics 2000, 295: 58-66. PMID: 10991961.Peer-Reviewed Original ResearchConceptsMesoprefrontal DA neuronsDA neuronsLocal infusionNicotinic acetylcholine receptor stimulationMesoprefrontal dopamine neuronsMesoprefrontal dopamine systemEndogenous opioid peptidesVentral tegmental areaHigh comorbid ratesNicotine-pretreated ratsMedial prefrontal cortexDA metabolismNicotinic modulationCortical dysfunctionNicotine administrationCigarette smokingSite of actionStress-induced statesNicotine pretreatmentDA dysregulationDopamine neuronsSystemic administrationTegmental areaDA dysfunctionCognitive dysfunction