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 basis
2022
Animal Models to Investigate the Impact of Flavors on Nicotine Addiction and Dependence
Bagdas D, Kebede N, Zepei AM, Harris L, Minanov K, Picciotto MR, Addy NA. Animal Models to Investigate the Impact of Flavors on Nicotine Addiction and Dependence. Current Neuropharmacology 2022, 20: 2175-2201. PMID: 35611777, PMCID: PMC9886843, DOI: 10.2174/1570159x20666220524120231.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsElectronic Nicotine Delivery SystemsFlavoring AgentsHumansModels, AnimalNicotineTobacco Use Disorder
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
2019
Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine
Lee AM, Calarco CA, McKee SA, Mineur YS, Picciotto MR. Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine. Genes Brain & Behavior 2019, 19: e12601. PMID: 31364813, PMCID: PMC8045136, DOI: 10.1111/gbb.12601.Peer-Reviewed Original ResearchConceptsStress-induced reinstatementEffects of guanfacinePlace preferenceFemale miceInfralimbic cortexArc immunoreactivityΑ2-adrenergic receptor agonistAnterior insulaNeurobiological mechanismsLateral central amygdalaNovel treatment optionsChamber preferencePlace preference acquisitionSex-dependent changesStress-induced relapseDose-response patternNucleus accumbens coreNicotine-dependent behaviorsSmoking occursTreatment optionsNicotine rewardReceptor agonistCentral amygdalaNeuronal activationPreclinical studies
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
Association of Cigarette Smoking With Interpersonal and Self-Directed Violence in a Large Community-Based Sample
Lewis AS, Oberleitner LM, Morgan PT, Picciotto MR, McKee SA. Association of Cigarette Smoking With Interpersonal and Self-Directed Violence in a Large Community-Based Sample. Nicotine & Tobacco Research 2015, 18: 1456-1462. PMID: 26718905, PMCID: PMC5942535, DOI: 10.1093/ntr/ntv287.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol-Related DisordersCigarette SmokingCross-Sectional StudiesFemaleHumansMaleMiddle AgedRisk FactorsTobacco Use DisorderViolenceConceptsCigarette smoking statusSmoking statusCigarette smokingSelf-directed violenceRisk factorsDaily smokersViolence risk assessmentWave 1Substance useFormer cigarette smokersFormer daily smokersDaily cigarette smokingMajor risk factorNational Epidemiological SurveyCommunity-based sampleLogistic regression modelsRelevant demographic covariatesViolence risk factorsCessation strategiesCigarette smokersPsychiatric diagnosisEpidemiological surveySmokersSmokingAdult subjectsMood 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
2013
Differential 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 interneuronsMolecules 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 behaviorsSmokeVareniclineNicotine, Striatum, and Reward
Addy NA, Picciotto MR. Nicotine, Striatum, and Reward. Biological Psychiatry 2013, 73: 205-206. PMID: 23337022, DOI: 10.1016/j.biopsych.2012.11.001.Peer-Reviewed Original Research
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 subunitNicotinic Regulation of Energy Homeostasis
Zoli M, Picciotto MR. Nicotinic Regulation of Energy Homeostasis. Nicotine & Tobacco Research 2012, 14: 1270-1290. PMID: 22990212, PMCID: PMC3611985, DOI: 10.1093/ntr/nts159.Peer-Reviewed Original ResearchConceptsEnergy homeostasisCellular targetsPossible molecular targetsPrimary psychoactive substanceCell typesNicotinic acetylcholine receptor subtypesEnergy metabolismAcetylcholine receptor subtypesAbility of nicotineEffects of nicotineRegulation of feedingMolecular targetsFunctional featuresRegulationNicotinic regulationHomeostasisReceptor subtypesNAChR subtypesTobacco smokeBody weightNeuroendocrine systemRecent studiesNicotineMetabolismMammals
2011
Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence
Xie P, Kranzler HR, Krauthammer M, Cosgrove KP, Oslin D, Anton RF, Farrer LA, Picciotto MR, Krystal JH, Zhao H, Gelernter J. Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence. Biological Psychiatry 2011, 70: 528-536. PMID: 21683344, PMCID: PMC3199609, DOI: 10.1016/j.biopsych.2011.04.017.Peer-Reviewed Original ResearchThe Galanin Receptor 1 Gene Associates with Tobacco Craving in Smokers Seeking Cessation Treatment
Lori A, Tang Y, O'Malley S, Picciotto MR, Wu R, Conneely KN, Cubells JF. The Galanin Receptor 1 Gene Associates with Tobacco Craving in Smokers Seeking Cessation Treatment. Neuropsychopharmacology 2011, 36: 1412-1420. PMID: 21430647, PMCID: PMC3096810, DOI: 10.1038/npp.2011.25.Peer-Reviewed Original ResearchMeSH KeywordsAdultComputational BiologyFemaleGenome-Wide Association StudyGenotypeHumansLinkage DisequilibriumMaleMiddle AgedPolymorphism, Single NucleotidePsychiatric Status Rating ScalesPsychological TestsReceptor, Galanin, Type 1Severity of Illness IndexSmoking CessationSurveys and QuestionnairesTobacco Use DisorderConceptsNicotine dependenceSingle nucleotide polymorphismsUseful therapeutic targetAddiction-related behaviorsFagerström scalePreclinical evidenceCessation treatmentPharmacological treatmentCessation trialCC subjectsTobacco cravingWithdrawal ScaleFTND scoreTC genotypeTherapeutic targetGalaninGene associatesSmokersSmokingBehavioral parametersSeverityGenetic association studiesSubjectsTreatmentScores
2010
Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis
Mineur YS, Picciotto MR. Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis. Trends In Pharmacological Sciences 2010, 31: 580-586. PMID: 20965579, PMCID: PMC2991594, DOI: 10.1016/j.tips.2010.09.004.Peer-Reviewed Original ResearchConceptsEffects of nicotineDepressive symptomsNeuronal nAChRsNovel antidepressant medicationsDepression-like behaviorMajor depressive disorderNicotinic acetylcholine receptorsAntidepressant medicationNicotine receptorsCholinergic systemDepressive disorderCholinergic hypothesisPreclinical studiesNicotinic drugsPharmacological agentsNicotinic agentsAcetylcholine receptorsEndogenous neurotransmittersSymptomsNAChRsNicotineSmokingDepressed individualsAcetylcholineReceptors
2009
Localized low‐level re‐expression of high‐affinity mesolimbic nicotinic acetylcholine receptors restores nicotine‐induced locomotion but not place conditioning
Mineur YS, Brunzell DH, Grady SR, Lindstrom JM, McIntosh JM, Marks MJ, King SL, Picciotto MR. Localized low‐level re‐expression of high‐affinity mesolimbic nicotinic acetylcholine receptors restores nicotine‐induced locomotion but not place conditioning. Genes Brain & Behavior 2009, 8: 257-266. PMID: 19077117, PMCID: PMC2672109, DOI: 10.1111/j.1601-183x.2008.00468.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConditioning, PsychologicalCyclic AMP Response Element-Binding ProteinDopamineGamma-Aminobutyric AcidGene Expression RegulationLocomotionMiceMice, Inbred C57BLMice, TransgenicNicotineNicotinic AgonistsPhosphorylationPresynaptic TerminalsReceptors, NicotinicRewardSynaptosomesTobacco Use DisorderVentral Tegmental AreaConceptsVentral tegmental areaGamma-aminobutyric acidNicotinic acetylcholine receptorsCyclic AMP response element binding proteinTegmental areaPlace preferenceTransgenic miceAcetylcholine receptorsBeta2 knockout micePedunculopontine tegmental areaSystemic nicotine administrationHigh-affinity nAChRsLaterodorsal tegmental nucleusNicotine place preferenceNicotinic partial agonistPlace preference testingDifferent neuronal subtypesAMP response element binding proteinTotal CREB levelsResponse element-binding proteinDA neuronsCholinergic neuronsNicotine administrationSystemic nicotineSmoking cessationNucleus Accumbens CREB Activity is Necessary for Nicotine Conditioned Place Preference
Brunzell DH, Mineur YS, Neve RL, Picciotto MR. Nucleus Accumbens CREB Activity is Necessary for Nicotine Conditioned Place Preference. Neuropsychopharmacology 2009, 34: 1993-2001. PMID: 19212318, PMCID: PMC2709692, DOI: 10.1038/npp.2009.11.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConditioning, PsychologicalCuesCyclic AMP Response Element-Binding ProteinDecision MakingDose-Response Relationship, DrugDown-RegulationGene Transfer TechniquesMaleMiceMice, Inbred C57BLNicotineNicotinic AgonistsNucleus AccumbensPhosphorylationRewardSynaptic TransmissionTobacco Use DisorderUp-RegulationConceptsCyclic AMP response element binding proteinNAc shellPlace preferenceNicotine CPPCREB activityModulation of cocaineCREB activationNicotine place preferenceAbility of nicotineAbsence of nicotineCue-induced responsesDominant-negative CREB constructNicotinic acetylcholine receptorsAMP response element binding proteinLevels of CREBTranscription factor cyclic AMP response element binding proteinViral-mediated gene transferRange of dosesActivation of intracellularNicotine exposureMorphine rewardC57BL/6J miceNicotine rewardDopamine neuronsLong-term consequences
2008
Molecular Mechanisms Underlying the Motivational Effects of Nicotine
Brunzell DH, Picciotto MR. Molecular Mechanisms Underlying the Motivational Effects of Nicotine. Nebraska Symposium On Motivation 2008, 55: 17-30. PMID: 19013937, PMCID: PMC3594851, DOI: 10.1007/978-0-387-78748-0_3.Peer-Reviewed Original ResearchVoluntary oral nicotine intake in mice down-regulates GluR2 but does not modulate depression-like behaviors
Vieyra-Reyes P, Picciotto MR, Mineur YS. Voluntary oral nicotine intake in mice down-regulates GluR2 but does not modulate depression-like behaviors. Neuroscience Letters 2008, 434: 18-22. PMID: 18261852, PMCID: PMC2757003, DOI: 10.1016/j.neulet.2008.01.021.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnimalsAnxiety DisordersBehavior, AnimalBrainCyclic AMP Response Element-Binding ProteinDepressive DisorderDown-RegulationGlutamic AcidMaleMiceMice, Inbred BALB CMice, Inbred C57BLMotor ActivityNeural PathwaysNicotineNicotinic AgonistsNucleus AccumbensReceptors, AMPARewardSynaptic TransmissionTobacco Use DisorderVentral Tegmental AreaVolitionConceptsCAMP response element-binding proteinDepression-like behaviorVentral tegmental areaNucleus accumbensMesolimbic systemNicotine preferenceChronic nicotine exposureDepression-related behaviorsNon-treated animalsBALB/cOral nicotine intakeCentral nervous systemResponse element-binding proteinNicotine exposureNicotine rewardMesolimbic dopamine projectionsTegmental areaNicotine intakeGlutamate receptorsDopamine projectionsElement-binding proteinNervous systemLocomotor activityMice C57BL/6JGluR1 levels