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 StatementsConceptsNicotine 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
2017
The Effect of Treatment with Guanfacine, an Alpha2 Adrenergic Agonist, on Dopaminergic Tone in Tobacco Smokers: An [11C]FLB457 PET Study
Sandiego CM, Matuskey D, Lavery M, McGovern E, Huang Y, Nabulsi N, Ropchan J, Picciotto MR, Morris ED, McKee SA, Cosgrove KP. The Effect of Treatment with Guanfacine, an Alpha2 Adrenergic Agonist, on Dopaminergic Tone in Tobacco Smokers: An [11C]FLB457 PET Study. Neuropsychopharmacology 2017, 43: 1052-1058. PMID: 28944773, PMCID: PMC5854798, DOI: 10.1038/npp.2017.223.Peer-Reviewed Original ResearchConceptsTobacco smokersGuanfacine treatmentPositron emission tomographyTobacco smokingDA releaseDopaminergic toneDopamine releaseAmphetamine-induced DA releaseTobacco smoking cessationCortical dopamine releaseExtrastriatal brain regionsAlpha2-adrenergic agonistExtrastriatal dopamine releaseEffect of treatmentBaseline BPNDSmoking cessationReceptor radiotracerAdrenergic agonistsPET scansAnimal modelsBrain regionsEmission tomographyPET studiesDopamine signalingSmokersEffect of doxazosin on stress reactivity and the ability to resist smoking
Verplaetse TL, Weinberger AH, Oberleitner LM, Smith KM, Pittman BP, Shi JM, Tetrault JM, Lavery ME, Picciotto MR, McKee SA. Effect of doxazosin on stress reactivity and the ability to resist smoking. Journal Of Psychopharmacology 2017, 31: 830-840. PMID: 28440105, PMCID: PMC5823502, DOI: 10.1177/0269881117699603.Peer-Reviewed Original ResearchConceptsTobacco cravingCortisol levelsSubsequent ad libitum smokingEffects of doxazosinAd libitum smokingNumber of cigarettesNicotine-motivated behaviorsSmoking lapse behaviorΑ1-adrenergic antagonistNicotine-deprived smokersTitration periodPreclinical findingsSmoking cessationNoradrenergic systemTreatment strategiesDoxazosinSmoking behaviorSmokingHuman laboratoryPhysiologic reactivityPilot studyStress reactivityEffects of stressCigarettesStress imagery
2016
CHRNA4 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
Targeting the Noradrenergic System for Gender-Sensitive Medication Development for Tobacco Dependence
Verplaetse TL, Weinberger AH, Smith PH, Cosgrove KP, Mineur YS, Picciotto MR, Mazure CM, McKee SA. Targeting the Noradrenergic System for Gender-Sensitive Medication Development for Tobacco Dependence. Nicotine & Tobacco Research 2015, 17: 486-495. PMID: 25762760, PMCID: PMC4432402, DOI: 10.1093/ntr/ntu280.Peer-Reviewed Original ResearchConceptsSmoking cessationNoradrenergic systemClinical evidenceTobacco dependenceNoradrenergic activityMedication developmentPoor smoking cessation outcomesCause of morbiditySmoking cessation outcomesStress reactivitySex-specific mechanismsLower quit ratesNicotine-related reinforcementCurrent medicationsMedication effectivenessNicotine reinforcementCessation outcomesNoradrenergic agentsQuit ratesTreatment strategiesTobacco useNoradrenergic compoundsSmoking outcomesTreatment developmentWomen
2013
Molecules 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 ResearchConceptsTobacco smokingNicotine reinforcementTobacco smokeNicotine addictionMultiple brain circuitsSymptoms of anxietyFuture therapeutic developmentSmoking cessationNicotine receptorsAdult smokingDevelopmental exposureSmokingNew treatmentsBrain circuitsTherapeutic developmentCellular basisWidespread addictionCircuit basisCessationBiological basisAddictionBehavioral studiesNumber of behaviorsSmokeVarenicline
2011
Nicotine Decreases Food Intake Through Activation of POMC Neurons
Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gündisch D, Diano S, De Biasi M, Horvath TL, Gao XB, Picciotto MR. Nicotine Decreases Food Intake Through Activation of POMC Neurons. Science 2011, 332: 1330-1332. PMID: 21659607, PMCID: PMC3113664, DOI: 10.1126/science.1201889.Peer-Reviewed Original ResearchConceptsFood intakePOMC neuronsNicotine decreases food intakeDecrease food intakePro-opiomelanocortin (POMC) neuronsΑ3β4 nicotinic acetylcholine receptorsHypothalamic melanocortin systemNicotine-induced decreasesMelanocortin-4 receptorNicotinic acetylcholine receptorsAnorexic effectDecrease appetiteSmoking cessationSynaptic mechanismsMelanocortin systemNovel treatmentsBody weightAcetylcholine receptorsNeurobiological mechanismsNeuronsIntakeSubsequent activationAppetiteActivationReceptors
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 cessation
2006
Nicotine withdrawal increases body weight, neuropeptide Y and Agouti-related protein expression in the hypothalamus and decreases uncoupling protein-3 expression in the brown adipose tissue in high-fat fed mice
Fornari A, Pedrazzi P, Lippi G, Picciotto MR, Zoli M, Zini I. Nicotine withdrawal increases body weight, neuropeptide Y and Agouti-related protein expression in the hypothalamus and decreases uncoupling protein-3 expression in the brown adipose tissue in high-fat fed mice. Neuroscience Letters 2006, 411: 72-76. PMID: 17052838, DOI: 10.1016/j.neulet.2006.10.014.Peer-Reviewed Original ResearchMeSH KeywordsAdipose Tissue, BrownAgouti Signaling ProteinAgouti-Related ProteinAnalysis of VarianceAnimalsBody WeightDietary FatsHypothalamusIntercellular Signaling Peptides and ProteinsIon ChannelsMaleMiceMice, Inbred C57BLMitochondrial ProteinsNeuropeptide YNicotineNicotinic AgonistsReceptors, Adrenergic, betaSubstance Withdrawal SyndromeUncoupling Protein 3ConceptsNicotine withdrawalBrown adipose tissueBody weightNeuropeptide YAdipose tissueOrexigenic peptides neuropeptide YHigh-fat fed miceChronic nicotine treatmentPeptides neuropeptide YHigh-fat dietAbility of nicotineBody weight regulationProtein 3 expressionAnorectic effectNicotine treatmentSmoking cessationFat dietFed miceHuman smokersNormal rodentsWeight regulationIncreased expressionProtein 3Protein expressionExposure results
2003
Nicotine as a modulator of behavior: beyond the inverted U
Picciotto MR. Nicotine as a modulator of behavior: beyond the inverted U. Trends In Pharmacological Sciences 2003, 24: 493-499. PMID: 12967775, DOI: 10.1016/s0165-6147(03)00230-x.Peer-Reviewed Original ResearchConceptsNeuronal pathwaysEffects of nicotineNicotinic acetylcholine receptorsNeurotransmitter release studiesSmoking cessationNicotine reinforcementOccasional smokingKnockout mouse studiesSmoking behaviorAnimal studiesAcetylcholine receptorsDifferent subtypesMouse studiesBehavioral effectsNew interventionsNicotineElectrophysiological experimentsActivation stateRecent dataBehavioral responsesModulator of behaviorSmokingPathwaySubtypesReceptors