2020
Mechanisms of Nicotine Addiction
Picciotto MR, Kenny PJ. Mechanisms of Nicotine Addiction. Cold Spring Harbor Perspectives In Medicine 2020, 11: a039610. PMID: 32341069, PMCID: PMC8091956, DOI: 10.1101/cshperspect.a039610.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMembrane-spanning subunitsLigand-gated ion channelsTobacco smokingLung cancerTobacco dependenceExpression of α5Nicotine addictionGene clusterGenetic variationNeuronal nicotinic acetylcholine receptorsΑ-subunitSmoking-associated diseasesΒ-subunitTobacco smoking habitsNicotinic acetylcholine receptorsEffects of nicotineSubunitsProperties of nicotineIon channelsRecent insightsΒ4 subunitΒ2 subunitMammalian brainSmoking habitsCessation agents
2014
Rare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors
McClure-Begley TD, Papke RL, Stone KL, Stokes C, Levy AD, Gelernter J, Xie P, Lindstrom J, Picciotto MR. Rare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors. Journal Of Pharmacology And Experimental Therapeutics 2014, 348: 410-420. PMID: 24385388, PMCID: PMC3935145, DOI: 10.1124/jpet.113.209767.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsRare variantsSingle amino acid substitutionLaevis oocytesAmino acid substitutionsΑ4β2 nAChRsAcetylcholine receptorsIntracellular interactomesHEK-293 cellsX. laevis oocytesProteomic analysisGenetic variationHuman α4β2 nAChRsXenopus laevis oocytesVoltage-clamp electrophysiologyNeuronal nicotinic acetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsSubcellular distributionAcid substitutionsΑ4 nAChR subunitCohort of smokersEffects of nicotineNAChR subunitsCommon variantsΑ4 nAChR
2013
Exploring the Nicotinic Acetylcholine Receptor-Associated Proteome with iTRAQ and Transgenic Mice
McClure-Begley TD, Stone KL, Marks MJ, Grady SR, Colangelo CM, Lindstrom JM, Picciotto MR. Exploring the Nicotinic Acetylcholine Receptor-Associated Proteome with iTRAQ and Transgenic Mice. Genomics Proteomics & Bioinformatics 2013, 11: 207-218. PMID: 23891776, PMCID: PMC3806329, DOI: 10.1016/j.gpb.2013.05.005.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsPutative interacting proteinsΒ2 subunitMammalian central nervous systemAcetylcholine receptorsInteracting proteinProteomic analysisQuantitative proteomicsCytoskeletal rearrangementsIsobaric tagsNeuronal nicotinic acetylcholine receptorsCalcium signalingAbsolute quantitationΑ4β2 nAChRsProteinReduced expressionΒ2 subunit expressionPotential targetCentral nervous systemSubunitsExpressionPrincipal receptorTransgenic miceSubunit expressionΑ4
2012
Molecular Mechanisms Underlying Behaviors Related to Nicotine Addiction
Picciotto MR, Kenny PJ. Molecular Mechanisms Underlying Behaviors Related to Nicotine Addiction. Cold Spring Harbor Perspectives In Medicine 2012, 3: a012112. PMID: 23143843, PMCID: PMC3530035, DOI: 10.1101/cshperspect.a012112.Peer-Reviewed Original ResearchConceptsMembrane-spanning subunitsLigand-gated ion channelsTobacco smokingLung cancerTobacco dependenceNicotine addictionCHRNB4 gene clusterExpression of α5Neuronal nicotinic acetylcholine receptorsGene clusterSmoking-associated diseasesGenetic variationTobacco smoking habitsEffects of nicotineMolecular mechanismsΑ-subunitProperties of nicotineΒ-subunitNicotinic acetylcholine receptorsSubunitsIon channelsSmoking habitsRecent insightsΒ4 subunitΒ2 subunit
2004
Alteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor
Harrist A, Beech RD, King SL, Zanardi A, Cleary MA, Caldarone BJ, Eisch A, Zoli M, Picciotto MR. Alteration of hippocampal cell proliferation in mice lacking the β2 subunit of the neuronal nicotinic acetylcholine receptor. Synapse 2004, 54: 200-206. PMID: 15472930, DOI: 10.1002/syn.20081.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsHippocampal cell proliferationAcetylcholine receptorsCell proliferationNeuronal nicotinic acetylcholine receptorsNeurotrophic factor BDNFAdult hippocampal neurogenesisHippocampus of miceAge-matched controlsGranule cell layerCellular proliferationPlasma corticosterone levelsHippocampal-dependent tasksGranule cell proliferationHippocampal proliferationHippocampal neurogenesisEndogenous acetylcholineAge-related declineDentate gyrusNeuronal survivalAbnormal myelinationCorticosterone levelsNormal agingYoung adultsApoptotic cell death
2002
Nicotinic receptors in aging and dementia
Picciotto MR, Zoli M. Nicotinic receptors in aging and dementia. Developmental Neurobiology 2002, 53: 641-655. PMID: 12436427, DOI: 10.1002/neu.10102.Peer-Reviewed Original ResearchConceptsNicotinic agonistsCognitive functionNeuronal nicotinic acetylcholine receptorsDevelopment of dementiaNicotinic acetylcholine receptorsCholinergic markersCholinergic functionNeuronal degenerationNicotinic receptorsEpidemiological studiesNicotinic functionAnimal studiesNeurodegenerative illnessesAcetylcholine receptorsCognitive deficitsDementiaNeurodegenerative diseasesImpaired subjectsDistinct actionsPatientsAgonistsDiseaseNicotineReceptorsSmoking
2000
5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors
Mukhin A, Gündisch D, Horti A, Koren A, Tamagnan G, Kimes A, Chambers J, Vaupel D, King S, Picciotto M, Innis R, London E. 5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors. Molecular Pharmacology 2000, 57: 642-649. PMID: 10692507, DOI: 10.1124/mol.57.3.642.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAlpha4beta2 nAChRsAcetylcholine receptorsNeuronal nicotinic acetylcholine receptorsAffinity of epibatidineRat adrenal glandMuscle-type nAChRsSubtype-selective ligandsAlpha4beta2 subtypeAdrenal glandRat brainSelective radioligandBrain regionsNAChRsBeta4 subunitsRadioiodinated ligandBeta2 subunitVivo studiesEpibatidineVivo experimentsHuman brainSubtypesRadioligandBrainReceptors
1998
Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine
Picciotto M, Zoli M, Rimondini R, Léna C, Marubio L, Pich E, Fuxe K, Changeux J. Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. Nature 1998, 391: 173-177. PMID: 9428762, DOI: 10.1038/34413.Peer-Reviewed Original ResearchMeSH Keywords3,4-Dihydroxyphenylacetic AcidAcetylcholineAnimalsBinding SitesCarrier ProteinsCocaineConditioning, OperantDopamineDopamine Plasma Membrane Transport ProteinsHomovanillic AcidIn Vitro TechniquesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiceMice, Inbred C57BLMice, Inbred DBAMice, KnockoutMicrodialysisMotor ActivityNerve Tissue ProteinsNicotineNucleus AccumbensPatch-Clamp TechniquesReceptors, NicotinicSecond Messenger SystemsSubstantia NigraVentral Tegmental AreaConceptsProperties of nicotineAcetylcholine receptorsVentral striatumΒ2 subunitNeuronal nicotinic acetylcholine receptorsMesencephalic dopaminergic neuronsEffects of nicotineWild-type micePatch-clamp recordingsMesolimbic dopamine systemNicotinic acetylcholine receptorsDrugs of abuseDopaminergic neuronsMesolimbic systemDopamine releaseDopamine systemMutant miceMiceNicotineNeurotransmitter dopamineStriatumReceptorsNeuronsReleaseBrain
1995
Promoter elements conferring neuron-specific expression of the β2-subunit of the neuronal nicotinic acetylcholine receptor studiedin vitro and in transgenic mice
Bessis A, Salmon A, Zoli M, Le Novère N, Picciotto M, Changeux J. Promoter elements conferring neuron-specific expression of the β2-subunit of the neuronal nicotinic acetylcholine receptor studiedin vitro and in transgenic mice. Neuroscience 1995, 69: 807-819. PMID: 8596650, DOI: 10.1016/0306-4522(95)00303-z.Peer-Reviewed Original ResearchConceptsSpatio-temporal expression patternsFunctional E-boxesCell-specific transcriptionNeuron-specific transcriptionSite-directed mutagenesisTransient transfection assaysNeuron-specific expressionNeuronal genesRE1 sequenceTranscribed regionDeletion analysisE-boxRegulatory elementsPromoter elementsUpstream sequencesTransgenic miceTransfection assaysReporter geneRepressor elementExpression patternsNeuronal nicotinic acetylcholine receptorsGenesNicotinic acetylcholine receptorsRegulatory propertiesTranscriptionAbnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain
Picciotto M, Zoli M, Léna C, Bessis A, Lallemand Y, LeNovère N, Vincent P, Pich E, Brûlet P, Changeux J. Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature 1995, 374: 65-67. PMID: 7870173, DOI: 10.1038/374065a0.Peer-Reviewed Original ResearchConceptsHigh-affinity nicotine receptorsNeuronal nicotinic acetylcholine receptorsBrains of miceΒ2-/- miceNicotinic acetylcholine receptorsThalamic neuronsNicotine applicationFunctional nAChRsNicotine receptorsBrain slicesNicotinic subunitsAbnormal avoidanceAcetylcholine receptorsAspects of behaviorHigh-affinity binding sitesMutant miceElectrophysiological recordingsPassive avoidanceAssociative memoryMiceNicotineNeuronal nicotinic subunitsNon-mutant siblingsBrainReceptors