2023
Nicotine addiction: More than just dopamine
Kim K, Picciotto M. Nicotine addiction: More than just dopamine. Current Opinion In Neurobiology 2023, 83: 102797. PMID: 37832393, PMCID: PMC10842238, DOI: 10.1016/j.conb.2023.102797.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsDopamineFemaleHumansMaleNicotineNicotinic AgonistsReceptors, NicotinicTobacco Use DisorderConceptsNicotine addictionImportant public health problemAnti-tobacco messagingNicotine-induced behaviorsPublic health problemReward-related behaviorsNovel glutamateDopaminergic mechanismsSmoking cessationNicotine reinforcementMesolimbic systemNicotine seekingRecent studiesTherapeutic targetNicotine aversionHealth problemsActive investigationAdditional pathwaysSex differencesNicotine vapingMolecular mechanismsWithdrawalAddictionPathwayMolecular basisPathophysiology 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
2020
Effects of nicotine on DARPP-32 and CaMKII signaling relevant to addiction
Lee AM, Picciotto MR. Effects of nicotine on DARPP-32 and CaMKII signaling relevant to addiction. Advances In Pharmacology 2020, 90: 89-115. PMID: 33706940, PMCID: PMC8008986, DOI: 10.1016/bs.apha.2020.09.002.Peer-Reviewed Original ResearchConceptsKey intracellular signaling cascadesIntracellular signaling cascadesDependent kinase IIPaul GreengardSignaling cascadesKinase IINicotine-dependent behaviorsNicotinic acetylcholine receptorsSecond messenger systemsNeuronal signalingInitial characterizationDARPP-32ProteinMessenger systemsAcetylcholine receptorsSignalingRoleCaMKIIGreengardNicotine addictionCascadeImmunohistochemical workDiscoveryReceptorsCAMPHippocampal knockdown of α2 nicotinic or M1 muscarinic acetylcholine receptors in C57BL/6J male mice impairs cued fear conditioning
Mineur YS, Ernstsen C, Islam A, Maibom KL, Picciotto MR. Hippocampal knockdown of α2 nicotinic or M1 muscarinic acetylcholine receptors in C57BL/6J male mice impairs cued fear conditioning. Genes Brain & Behavior 2020, 19: e12677. PMID: 32447811, PMCID: PMC8018799, DOI: 10.1111/gbb.12677.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConditioning, OperantCuesFearGene DeletionHEK293 CellsHippocampusHumansMaleMiceMice, Inbred C57BLReceptor, Muscarinic M1Receptors, NicotinicConceptsFear learningShort-term learningNumber of paradigmsCued fearLight/dark boxFear conditioningContextual memoryStress-related behaviorsStress-induced reactivityTerm learningBrain circuitsRobust effectM1 mAChRHippocampal acetylcholineM1 muscarinic ACh receptorsNovelty-suppressed feeding testLearningMemoryDark boxHippocampus of malesM1 muscarinic acetylcholine receptorHippocampal knockdownFearMuscarinic ACh receptorsGroups of mice
2019
Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies
Lewis AS, Picciotto MR. Regulation of aggressive behaviors by nicotinic acetylcholine receptors: Animal models, human genetics, and clinical studies. Neuropharmacology 2019, 167: 107929. PMID: 32058178, PMCID: PMC7080580, DOI: 10.1016/j.neuropharm.2019.107929.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAggressionAnimalsClinical Trials as TopicHuman GeneticsHumansModels, AnimalNicotineNicotinic AgonistsReceptors, NicotinicConceptsNicotinic acetylcholine receptorsClinical studiesAnimal modelsAcetylcholine receptorsNeuropsychiatric disordersAggressive behaviorEffects of nAChRsAlpha 7 nAChRsSignificant side effectsHuman laboratory studiesLigand-gated ion channelsPsychopharmacological treatmentSide effectsMultiple key questionsHuman patientsNicotine NeuropharmacologyPredatory aggressionCHRNA7 geneHuman geneticsHuman genetic studiesPatientsNAChRsSevere aggressionIon channelsReceptorsNicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake
Calarco CA, Picciotto MR. Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake. Nicotine & Tobacco Research 2019, 22: 152-163. PMID: 30690485, PMCID: PMC7297099, DOI: 10.1093/ntr/ntz010.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsFood intakeNicotinic acetylcholine receptorsWeight gainBody weightPreclinical workAcetylcholine receptorsPost-cessation weight gainOrexigenic agouti-related peptideAnorexigenic proopiomelanocortin (POMC) neuronsNicotine replacement therapyAgouti-related peptideNicotinic agonist cytisineAbility of nicotineLower body weightProopiomelanocortin neuronsNicotine administrationHypothalamic circuitsReplacement therapyArcuate nucleusNicotine effectsNicotine actsAgonist cytisineAverage weight gainTobacco useRodent models
2017
Menthol disrupts nicotine’s psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice
Fait BW, Thompson DC, Mose TN, Jatlow P, Jordt SE, Picciotto MR, Mineur YS. Menthol disrupts nicotine’s psychostimulant properties in an age and sex-dependent manner in C57BL/6J mice. Behavioural Brain Research 2017, 334: 72-77. PMID: 28743602, PMCID: PMC5580257, DOI: 10.1016/j.bbr.2017.07.027.Peer-Reviewed Original ResearchConceptsAdult male miceNicotine intakeMale micePsychostimulant effectsPsychostimulant propertiesHome cage locomotor activitySex-dependent mannerSex-dependent mechanismsBlood levelsAdolescent miceFemale miceLocomotor stimulationLocomotor activityNicotine sensitivityAge groupsE-cigarettesMiceIntakeSignificant decreaseNicotineAgeSexBehavioral changesAdultsSpecific mechanisms
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 functionCHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation
Esterlis I, Hillmer AT, Bois F, Pittman B, McGovern E, O’Malley S, Picciotto MR, Yang BZ, Gelernter J, Cosgrove KP. CHRNA4 and ANKK1 Polymorphisms Influence Smoking-Induced Nicotinic Acetylcholine Receptor Upregulation. Nicotine & Tobacco Research 2016, 18: 1845-1852. PMID: 27611310, PMCID: PMC4978979, DOI: 10.1093/ntr/ntw081.Peer-Reviewed Original ResearchMeSH KeywordsAdultCase-Control StudiesCorpus StriatumFemaleHumansIodine RadioisotopesMalePolymorphism, Single NucleotideProtein Serine-Threonine KinasesReceptors, NicotinicSmokingSmoking CessationSmoking PreventionTobacco Use DisorderTomography, Emission-Computed, Single-PhotonUp-RegulationWhite PeopleConceptsSmoking-induced changesWeeks of abstinenceNAChR availabilitySmoking cessationNicotine dependenceSex-matched nonsmokersTomography brain scanSingle nucleotide polymorphismsNicotinic acetylcholine receptorsSingle photon emissionDays of abstinenceNonsmoker levelsTobacco smokingReceptor upregulationBlood samplesAcetylcholine receptorsBrain scansCHRNA4 variantsCortical regionsSmokersCarrier statusExtended abstinenceAbstinencePersonalized programsNonsmokers
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 infusionModulation of aggressive behavior in mice by nicotinic receptor subtypes
Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR. Modulation of aggressive behavior in mice by nicotinic receptor subtypes. Biochemical Pharmacology 2015, 97: 488-497. PMID: 26212554, PMCID: PMC4600457, DOI: 10.1016/j.bcp.2015.07.019.Peer-Reviewed Original ResearchConceptsAcute nicotine administrationNicotine administrationHypolocomotor effectNicotinic acetylcholine receptor agonist nicotineAgonist GTS-21Nicotinic receptor subtypesAnti-aggressive propertiesDihydro-β-erythroidineBALB/cNeurobiology of aggressionSocial interaction timeCurrent pharmacotherapyAntagonist methyllycaconitineC57BL/6 miceWorse outcomesGTS-21Receptor subtypesPathological aggressionAgonist nicotineΑ7 nAChRsSpecific treatmentSide effectsPharmacological studiesNeuropsychiatric conditionsNicotineMood 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
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
In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia
Esterlis I, Ranganathan M, Bois F, Pittman B, Picciotto MR, Shearer L, Anticevic A, Carlson J, Niciu MJ, Cosgrove KP, D’Souza D. In Vivo Evidence for β2 Nicotinic Acetylcholine Receptor Subunit Upregulation in Smokers as Compared With Nonsmokers With Schizophrenia. Biological Psychiatry 2013, 76: 495-502. PMID: 24360979, PMCID: PMC4019710, DOI: 10.1016/j.biopsych.2013.11.001.Peer-Reviewed Original ResearchConceptsLower β2Negative symptomsCortical regionsLower receptor availabilitySelf-medicate symptomsComparison groupLower negative symptomsHigh β2Executive controlExecutive functionNicotine cravingSex-matched comparison subjectsMood assessmentBrain regionsWorse performanceComparison subjectsDiagnosis interactionLimited brain regionsNicotinic acetylcholine receptorsSchizophreniaSingle photon emissionNAChR availabilityActive smokingTobacco smokingPoor outcomeDifferential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule
Peng C, Stokes C, Mineur YS, Picciotto MR, Tian C, Eibl C, Tomassoli I, Guendisch D, Papke RL. Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule. Journal Of Pharmacology And Experimental Therapeutics 2013, 347: 424-437. PMID: 23959137, PMCID: PMC3807070, DOI: 10.1124/jpet.113.206904.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAzocinesBehavior, AnimalBenzazepinesBrainBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugDrug Partial AgonismHEK293 CellsHumansMaleMembrane PotentialsMiceMolecular StructureNicotinic AgonistsOocytesPatch-Clamp TechniquesQuinolizinesQuinoxalinesRatsRats, Sprague-DawleyReceptors, NicotinicTobacco Use DisorderVareniclineXenopus laevisConceptsPartial agonistLGN neuronsMouse tail suspension testLateral geniculate nucleus neuronsNicotinic acetylcholine receptor functionPartial agonist therapiesTail suspension testStratum radiatum interneuronsSmoking cessation drugNicotinic partial agonistAcetylcholine receptor functionHuman embryonic kidney 293 cellsSteady-state activationAgonist therapyRadiatum interneuronsEmbryonic kidney 293 cellsCessation drugsNucleus neuronsSuspension testΑ7 currentsNicotine addictionSide effectsVareniclineΑ4β2 nAChRsSR interneuronsExploring 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 expressionΑ4Nicotinic 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 stimulationChanges in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography
Hannestad JO, Cosgrove KP, DellaGioia NF, Perkins E, Bois F, Bhagwagar Z, Seibyl JP, McClure-Begley TD, Picciotto MR, Esterlis I. Changes in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography. Biological Psychiatry 2013, 74: 768-776. PMID: 23773793, PMCID: PMC3805761, DOI: 10.1016/j.biopsych.2013.04.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzetidinesBipolar DisorderBrain ChemistryFemaleHumansMalePyridinesReceptors, NicotinicSmokingTomography, Emission-Computed, Single-PhotonConceptsBipolar depressionControl subjectsCholinergic systemSingle photon emissionBipolar disorderAge-matched control subjectsEndogenous acetylcholine levelsNew treatment targetsNicotinic acetylcholine receptorsPhoton emissionLow receptor numbersClinical characteristicsEndogenous acetylcholineDepressive episodeAcetylcholine levelsTomography scanMajor depressionReceptor numberTemporal cortexNAChR numbersTreatment targetsAcetylcholine receptorsControl groupBrain regionsLower β2Morphine dependence and withdrawal induced changes in cholinergic signaling
Neugebauer NM, Einstein EB, Lopez MB, McClure-Begley TD, Mineur YS, Picciotto MR. Morphine dependence and withdrawal induced changes in cholinergic signaling. Pharmacology Biochemistry And Behavior 2013, 109: 77-83. PMID: 23651795, PMCID: PMC3690589, DOI: 10.1016/j.pbb.2013.04.015.Peer-Reviewed Original ResearchConceptsMedial habenulaMorphine dependenceCholinergic signalingInterpeduncular nucleusHigh-affinity nicotinic acetylcholine receptorsNicotinic acetylcholine receptor levelsEffects of cholinergicMorphine-dependent miceChronic morphine administrationAcetylcholine receptor levelsC-fos expressionC-Fos activationNicotinic acetylcholine receptorsDependent miceMorphine administrationMorphine withdrawalCholinergic drugsOpiate withdrawalCholinergic systemEpibatidine bindingReceptor levelsSomatic signsNeuronal activityAcetylcholine receptorsNAChR receptorMolecules and circuits involved in nicotine addiction: The many faces of smoking
Picciotto MR, Mineur YS. Molecules and circuits involved in nicotine addiction: The many faces of smoking. Neuropharmacology 2013, 76: 545-553. PMID: 23632083, PMCID: PMC3772953, DOI: 10.1016/j.neuropharm.2013.04.028.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAppetiteBrainDisease Models, AnimalHumansMood DisordersNicotineReceptors, NicotinicSmoking CessationTobacco Use DisorderConceptsTobacco smokingNicotine reinforcementTobacco smokeNicotine addictionMultiple brain circuitsSymptoms of anxietyFuture therapeutic developmentSmoking cessationNicotine receptorsAdult smokingDevelopmental exposureSmokingNew treatmentsBrain circuitsTherapeutic developmentCellular basisWidespread addictionCircuit basisCessationBiological basisAddictionBehavioral studiesNumber of behaviorsSmokeVarenicline