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
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 channelsReceptorsPerinatal 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 investigationTrialsInteraction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice
Mineur YS, Cahuzac EL, Mose TN, Bentham MP, Plantenga ME, Thompson DC, Picciotto MR. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology 2018, 43: 2118-2125. PMID: 29472646, PMCID: PMC6098039, DOI: 10.1038/s41386-018-0024-x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdrenergic alpha-AgonistsAlkaloidsAmygdalaAnimalsAnxietyAzocinesCholinesterase InhibitorsDepressionFemaleGene Knockdown TechniquesGuanfacineMaleMiceMice, Inbred C57BLNicotinic AgonistsNorepinephrineParasympathetic Nervous SystemQuinolizinesReceptors, Adrenergic, alpha-2Signal TransductionSympathetic Nervous SystemConceptsAntidepressant-like effectsNoradrenergic systemMale C57BL/6J miceDepression-related behaviorsDepression-like phenotypeNicotinic acetylcholine receptorsAntidepressant efficacyCholinergic interactionsNE terminalsC57BL/6J miceShRNA-mediated knockdownAgonist guanfacineAgonist cytisineClinical studiesSmoking relapseΑ2A receptorsAcute abstinenceBrain areasAcetylcholine receptorsAcetylcholineGuanfacineAmygdalaBehavioral effectsAnxiety disordersStress pathways
2017
Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors
Lewis AS, Pittenger ST, Mineur YS, Stout D, Smith PH, Picciotto MR. Bidirectional Regulation of Aggression in Mice by Hippocampal Alpha-7 Nicotinic Acetylcholine Receptors. Neuropsychopharmacology 2017, 43: 1267-1275. PMID: 29114104, PMCID: PMC5916354, DOI: 10.1038/npp.2017.276.Peer-Reviewed Original ResearchConceptsΑ7 nAChRsDentate gyrusNicotinic acetylcholine receptorsGTS-21Resident-intruder interactionsAlpha 7 nicotinic acetylcholine receptorAcetylcholine receptorsΑ7 nicotinic acetylcholine receptorExcitatory-inhibitory balancePromising therapeutic interventionGranule cell activityAggressive behaviorResident-intruder testHippocampal α7Wild-type controlsUnderlying neurobiological substratesGABAergic interneuronsMale micePotential neural circuitsRegulation of aggressionGranule cellsTherapeutic interventionsPartial agonistBrain regionsCell activityEffects of a nicotinic agonist on the Brief Psychiatric Rating Scale five-factor subscale model in schizophrenia
Lewis AS, Olincy A, Buchanan RW, Kem WR, Picciotto MR, Freedman R. Effects of a nicotinic agonist on the Brief Psychiatric Rating Scale five-factor subscale model in schizophrenia. Schizophrenia Research 2017, 195: 568-569. PMID: 29050790, PMCID: PMC6476180, DOI: 10.1016/j.schres.2017.10.016.Peer-Reviewed Original ResearchAccess 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 useEffects of varenicline on alcohol self-administration and craving in drinkers with depressive symptoms
Roberts W, Verplaetse TL, Moore K, Oberleitner L, Picciotto MR, McKee SA. Effects of varenicline on alcohol self-administration and craving in drinkers with depressive symptoms. Journal Of Psychopharmacology 2017, 31: 906-914. PMID: 28351203, PMCID: PMC5823265, DOI: 10.1177/0269881117699618.Peer-Reviewed Original ResearchConceptsDepressive symptomsAlcohol cravingAlcohol useEffects of vareniclineRole of nAChRsHuman laboratory studiesDSM-IV criteriaSymptoms of depressionAlcohol use disorderLaboratory testing sessionsMore depressive symptomsMedication pretreatmentPlasma levelsPriming doseVareniclineUse disordersTreatment moderatorsAlcohol consumptionDepression symptomsHeavy drinkersAlcohol usersDrinking taskSymptomsLess drinkingDrinkers
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 function
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 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
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 interneurons
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 subunitImpaired auditory discrimination learning following perinatal nicotine exposure or β2 nicotinic acetylcholine receptor subunit deletion
Horst NK, Heath CJ, Neugebauer NM, Kimchi EY, Laubach M, Picciotto MR. Impaired auditory discrimination learning following perinatal nicotine exposure or β2 nicotinic acetylcholine receptor subunit deletion. Behavioural Brain Research 2012, 231: 170-180. PMID: 22433585, PMCID: PMC3334440, DOI: 10.1016/j.bbr.2012.03.002.Peer-Reviewed Original ResearchConceptsAuditory stimulus processingStimulus processingAuditory discrimination learningUnderlying neurobiological mechanismsAuditory discrimination paradigmLow rates (DRL) taskPerinatal nicotine exposureAuditory discriminationGeneral deficitDiscrimination learningTask performanceNicotine exposureDiscrimination impairmentNeurobiological mechanismsMouse perinatal developmentDiscrimination paradigmRate taskDifferential reinforcementAdministration of nicotineTaskAuditory pathwayLearningNicotinic acetylcholine receptorsMaternal smokingProcessingNicotine-taking and nicotine-seeking in C57Bl/6J mice without prior operant training or food restriction
Yan Y, Pushparaj A, Gamaleddin I, Steiner RC, Picciotto MR, Roder J, Le Foll B. Nicotine-taking and nicotine-seeking in C57Bl/6J mice without prior operant training or food restriction. Behavioural Brain Research 2012, 230: 34-39. PMID: 22326373, PMCID: PMC3310267, DOI: 10.1016/j.bbr.2012.01.042.Peer-Reviewed Original ResearchConceptsNose-poke behaviorPrior operant trainingFood restrictionDose-response curveNicotine-seeking behaviorC57BL/6J miceIntermittent footshockFlat dose-response curveNaive C57BL/6J miceInjections of nicotineOperant trainingNicotine self-administration paradigmSelf-administration paradigmCue presentationSelf-administered salineNicotine groupNicotine reinforcementLight cue presentationPriming injectionsFR2 scheduleSecond consecutive dayConsecutive daysMiceDaily sessionsNicotine
2011
Decreased α4β2 nicotinic receptor number in the absence of mRNA changes suggests post‐transcriptional regulation in the spontaneously hypertensive rat model of ADHD
Wigestrand MB, Mineur YS, Heath CJ, Fonnum F, Picciotto MR, Walaas SI. Decreased α4β2 nicotinic receptor number in the absence of mRNA changes suggests post‐transcriptional regulation in the spontaneously hypertensive rat model of ADHD. Journal Of Neurochemistry 2011, 119: 240-250. PMID: 21824140, PMCID: PMC3171636, DOI: 10.1111/j.1471-4159.2011.07415.x.Peer-Reviewed Original ResearchMeSH KeywordsAconitineAnimalsAttention Deficit Disorder with HyperactivityAzetidinesBrain ChemistryBridged Bicyclo Compounds, HeterocyclicBungarotoxinsIn Vitro TechniquesKineticsMaleMembranesNicotinic AgonistsNicotinic AntagonistsProtein Processing, Post-TranslationalPyridinesRatsRats, Inbred SHRRats, Inbred WKYReceptors, NicotinicReverse Transcriptase Polymerase Chain ReactionRNA, MessengerThermodynamicsConceptsAttention-deficit/hyperactivity disorderQuantitative real-time PCRBrain regionsCerebellum of SHRWistar-Kyoto rat controlsHypertensive rat modelMRNA levelsNicotinic receptor numbersCentral nicotinic receptorsSpecific brain regionsAdditional brain regionsSHR brainHypertensive ratsRat modelReal-time PCRNicotinic receptorsReceptor numberEpidemiological studiesLevels of mRNAΑ4β2 nAChRsSHRWKYNAChRsHyperactivity disorderStrain differences