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
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 Statements
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 workDiscoveryReceptorsCAMP
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 StatementsConceptsNicotinic 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 channelsReceptorsVariability 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 studiesPerinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice
Lee AM, Picciotto MR. Perinatal nicotine exposure impairs learning of a skilled forelimb reaching task in male but not female adult mice. Behavioural Brain Research 2019, 367: 176-180. PMID: 30959127, PMCID: PMC6481625, DOI: 10.1016/j.bbr.2019.04.007.Peer-Reviewed Original ResearchConceptsNicotine exposureSingle-pellet reaching taskMotor tasksCortical synaptic plasticityPerinatal nicotine exposureDevelopmental nicotine exposureGross motor functionNicotine-treated animalsNicotine-induced changesFemale adult miceSkilled motor taskGross motor performanceAdverse outcomesMotor cortexFemale miceMale miceMotor functionSkilled forelimbPreclinical studiesControl animalsAdult miceImpaired learningSynaptic plasticityFemale pupsMorphologic changesNicotinic 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
2018
An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder
Lewis AS, van Schalkwyk GI, Lopez MO, Volkmar FR, Picciotto MR, Sukhodolsky DG. An Exploratory Trial of Transdermal Nicotine for Aggression and Irritability in Adults with Autism Spectrum Disorder. Journal Of Autism And Developmental Disorders 2018, 48: 2748-2757. PMID: 29536216, PMCID: PMC6394231, DOI: 10.1007/s10803-018-3536-7.Peer-Reviewed Original ResearchConceptsAutism spectrum disorderSpectrum disorderTransdermal nicotineDouble-blind crossover trialAggressive behaviorPreliminary efficacyAggressive symptomsSleep ratingsAggressionSubscale changesNicotinic acetylcholine receptorsNAChR agonistsPrimary outcomeNicotine treatmentCrossover trialExploratory trialΑ7 nAChRsAcetylcholine receptorsNicotineAdultsDisordersPlaceboNAChRsFurther investigationTrials
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 mechanismsAccess to nicotine in drinking water reduces weight gain without changing caloric intake on high fat diet in male C57BL/6J mice
Calarco CA, Lee S, Picciotto MR. Access to nicotine in drinking water reduces weight gain without changing caloric intake on high fat diet in male C57BL/6J mice. Neuropharmacology 2017, 123: 210-220. PMID: 28623168, PMCID: PMC5544033, DOI: 10.1016/j.neuropharm.2017.06.012.Peer-Reviewed Original ResearchConceptsHigh-fat dietCaloric intakeWeight gainFat dietFemale miceMale miceBody weightAdipose tissueEffects of HFDOverall caloric intakeAmphetamine-regulated transcriptNicotinic acetylcholine receptor subunitsLower body weightMelanin-concentrating hormoneSex-dependent mannerRegulation of agoutiChow-fed animalsAcetylcholine receptor subunitsNicotine administrationChronic consumptionArcuate nucleusNicotine dosesNicotine intakeFood intakeTobacco use
2016
Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism
Fan L, Balakrishna S, Jabba SV, Bonner PE, Taylor SR, Picciotto MR, Jordt SE. Menthol decreases oral nicotine aversion in C57BL/6 mice through a TRPM8-dependent mechanism. Tobacco Control 2016, 25: ii50. PMID: 27698211, PMCID: PMC5496986, DOI: 10.1136/tobaccocontrol-2016-053209.Peer-Reviewed Original ResearchConceptsSmokeless tobacco productsWild-type miceOral nicotineC57BL/6 miceTobacco productsNicotine aversionAversive effectsTwo-bottle choice drinkingTrigeminal sensory neuronsEffect of mentholProduct useMenthol concentrationOral mentholSensory neuronsAversive concentrationsMenthol receptorOral cavityMenthol effectsRespiratory irritationMiceNicotineTRPM8Oral irritantsIrritantsAversive tasteEvaluation 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 functionAn epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior
Jung Y, Hsieh LS, Lee AM, Zhou Z, Coman D, Heath CJ, Hyder F, Mineur YS, Yuan Q, Goldman D, Bordey A, Picciotto MR. An epigenetic mechanism mediates developmental nicotine effects on neuronal structure and behavior. Nature Neuroscience 2016, 19: 905-914. PMID: 27239938, PMCID: PMC4925298, DOI: 10.1038/nn.4315.Peer-Reviewed Original Research
2015
Modulation 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 conditionsNicotineReduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder
Van Schalkwyk GI, Lewis AS, Qayyum Z, Koslosky K, Picciotto MR, Volkmar FR. Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder. Journal Of Autism And Developmental Disorders 2015, 45: 3061-3066. PMID: 25982311, PMCID: PMC4755349, DOI: 10.1007/s10803-015-2471-0.Peer-Reviewed Original ResearchConceptsTransdermal nicotineNicotine administrationAutism spectrum disorderTransdermal nicotine administrationAdjunctive medicationsCurrent pharmacotherapyNicotine patchCholinergic dysfunctionEmergency medicationPreclinical studiesSpectrum disorderAnimal studiesAcetylcholinergic neurotransmissionNeuropsychiatric conditionsAggressive episodesMajor causeNicotineASD pathophysiologyMedicationsMorbidityFurther studiesAggression-related behaviorsAdministrationDisordersAdolescentsTargeting 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 developmentWomenMood 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
Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons
Mazei-Robison MS, Appasani R, Edwards S, Wee S, Taylor SR, Picciotto MR, Koob GF, Nestler EJ. Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons. PLOS ONE 2014, 9: e95962. PMID: 24755634, PMCID: PMC3995955, DOI: 10.1371/journal.pone.0095962.Peer-Reviewed Original ResearchConceptsVentral tegmental areaSoma sizeDopamine neuronsVentral tegmental area dopamine neuronsChronic opiate administrationAdditional drug classesDrug-specific mannerMorphological changesSelf-administer cocaineOpiate administrationTegmental areaDrug classesDA circuitsMesolimbic DA circuitSelf-AdministrationFiring rateSimilar morphological changesGeneral hallmarkNeuronsNicotineCocaineDrugsRecent findingsPrevious observationsNeuroplasticityRare 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