2023
Nicotinic regulation of microglia: potential contributions to addiction
Soares A, Picciotto M. Nicotinic regulation of microglia: potential contributions to addiction. Journal Of Neural Transmission 2023, 131: 425-435. PMID: 37778006, PMCID: PMC11189589, DOI: 10.1007/s00702-023-02703-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNeuroimmune signalingNicotine addictionΑ7 nicotinic acetylcholine receptorAnti-inflammatory cascadeAnti-inflammatory effectsEffects of nicotineAnti-inflammatory compoundsIntracellular calcium concentrationNicotinic acetylcholine receptorsMicroglial polarizationNicotinic regulationMicroglial activityMicroglial signalingImmunomodulatory effectsImmunosuppressive effectsWithdrawal symptomsCytokine releaseCircuit disruptionPreclinical literaturePreclinical studiesΑ7 nAChRsCircuit dysregulationNicotine dependenceMicrogliaAcetylcholine receptorsPathophysiology 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
Nicotine Pharmacology, Abuse, and Addiction
Miller M, Picciotto M. Nicotine Pharmacology, Abuse, and Addiction. 2022, 4083-4101. DOI: 10.1007/978-3-030-88832-9_157.ChaptersTobacco useDrugs of abuseNeuropsychiatric disordersGreat public health relevanceGreat public health concernMesolimbic dopamine systemPre-clinical studiesPublic health concernPublic health relevanceNicotinic acetylcholine receptorsIonotropic neurotransmitter receptorsPrimary psychoactive componentSubstantial health risksNicotine exposureNicotine actsSustained tobacco useNicotine pharmacologyRewarding effectsNicotine addictionDopamine systemNervous systemNeurotransmitter receptorsNicotine useAcetylcholine receptorsAddictive properties
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 workDiscoveryReceptorsCAMPMechanisms 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
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 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
2018
Evaluation of the Phosphoproteome of Mouse Alpha 4/Beta 2-Containing Nicotinic Acetylcholine Receptors In Vitro and In Vivo
Miller MB, Wilson RS, Lam TT, Nairn AC, Picciotto MR. Evaluation of the Phosphoproteome of Mouse Alpha 4/Beta 2-Containing Nicotinic Acetylcholine Receptors In Vitro and In Vivo. Proteomes 2018, 6: 42. PMID: 30326594, PMCID: PMC6313896, DOI: 10.3390/proteomes6040042.Peer-Reviewed Original ResearchProtein kinase APhosphorylation sitesPKA sitesHEK cellsNicotinic acetylcholine receptorsCalmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IIProtein kinase IIAcetylcholine receptorsKinase AKinase IIMouse brainSubunit phosphorylationNovel siteSubunitsAcute nicotine administrationΒ2 subunitMammalian brainCaMKIIPhosphorylationReceptor functionΑ4 subunitHuman brain tissueBeta 2Nicotine administrationMolecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus
Calarco CA, Li Z, Taylor SR, Lee S, Zhou W, Friedman JM, Mineur YS, Gotti C, Picciotto MR. Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus. European Journal Of Neuroscience 2018, 48: 1600-1619. PMID: 29791746, PMCID: PMC6251769, DOI: 10.1111/ejn.13966.Peer-Reviewed Original ResearchPOMC cellsArcuate nucleusFood intakeOrexigenic agouti-related peptideNicotinic acetylcholine receptor subtypesAnorexigenic pro-opiomelanocortin (POMC) neuronsDecrease food intakePro-opiomelanocortin (POMC) neuronsAcetylcholine receptor subtypesMRNA levelsAgouti-related peptideNicotinic agonist cytisineNicotinic acetylcholine receptorsSubunit mRNA levelsNeuronal cell typesAnorexigenic neuronsNicotinic regulationNicotinic modulationSmall hairpin RNAHypothalamic regionsReal-time PCRReceptor subtypesAgonist cytisineΑ7 subunitAcetylcholine receptorsAn 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 activityHippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice
Mineur YS, Mose TN, Blakeman S, Picciotto MR. Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice. British Journal Of Pharmacology 2017, 175: 1903-1914. PMID: 28264149, PMCID: PMC5979617, DOI: 10.1111/bph.13769.Peer-Reviewed Original ResearchConceptsDepression-like behaviorNicotinic ACh receptorsFemale miceMale miceCholinergic signalingACh receptorsΑ7 nAChRsSignificant antidepressant-like effectΑ7 nicotinic ACh receptorsEffect of α7Antidepressant-like effectsAgonist GTS-21Depression-related behaviorsC-Fos immunoreactivityACh receptor antagonistDepression-like phenotypeAnxiety-like behaviorNicotinic acetylcholine receptorsAnxiety-like phenotypeHippocampal α7Physostigmine administrationAntagonist methyllycaconitineReceptor antagonistSwim testGTS-21
2016
Nicotine Pharmacology, Abuse, and Addiction
Miller M, Picciotto M. Nicotine Pharmacology, Abuse, and Addiction. 2016, 3659-3677. DOI: 10.1007/978-1-4939-3474-4_157.ChaptersTobacco useDrugs of abuseNeuropsychiatric disordersGreat public health relevanceGreat public health concernMesolimbic dopamine systemPre-clinical studiesPublic health concernPublic health relevanceNicotinic acetylcholine receptorsIonotropic neurotransmitter receptorsPrimary psychoactive componentSubstantial health risksNicotine exposureNicotine actsSustained tobacco useNicotine pharmacologyRewarding effectsNicotine addictionDopamine systemNervous systemNeurotransmitter receptorsNicotine useAcetylcholine receptorsAddictive propertiesEvaluation 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
Mood 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 statesReceptorsDisordersNAChRsNicotineMoodAcetylcholine Acts through Nicotinic Receptors to Enhance the Firing Rate of a Subset of Hypocretin Neurons in the Mouse Hypothalamus through Distinct Presynaptic and Postsynaptic Mechanisms1,2
Zhou WL, Gao XB, Picciotto MR. Acetylcholine Acts through Nicotinic Receptors to Enhance the Firing Rate of a Subset of Hypocretin Neurons in the Mouse Hypothalamus through Distinct Presynaptic and Postsynaptic Mechanisms1,2. ENeuro 2015, 2: eneuro.0052-14.2015. PMID: 26322330, PMCID: PMC4551500, DOI: 10.1523/eneuro.0052-14.2015.Peer-Reviewed Original ResearchHypocretin neuronsMiniature EPSCsPostsynaptic nAChRsFiring rateHypocretin/orexin neuronsFrequency of mEPSCsAntagonism of nAChRsPhasic ACh releasePresence of atropineApplication of AChInternal calcium releaseNicotinic acetylcholine receptorsMouse brain slicesOne-thirdAddiction-related behaviorsPresynaptic AChPresynaptic nAChRsOrexin neuronsACh releaseGlutamatergic inputsPostsynaptic modulationPostsynaptic mechanismsMEPSC frequencyTonic activationBrain slicesNicotine Pharmacology, Abuse, and Addiction
Miller M, Picciotto M. Nicotine Pharmacology, Abuse, and Addiction. 2015, 1-19. DOI: 10.1007/978-1-4614-6434-1_157-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsTobacco useDrugs of abuseNeuropsychiatric disordersGreat public health relevanceGreat public health concernMesolimbic dopamine systemPre-clinical studiesPublic health concernPublic health relevanceNicotinic acetylcholine receptorsIonotropic neurotransmitter receptorsPrimary psychoactive componentSubstantial health risksNicotine exposureNicotine actsSustained tobacco useNicotine pharmacologyRewarding effectsNicotine addictionDopamine systemNervous systemNeurotransmitter receptorsNicotine useAcetylcholine receptorsAddictive properties
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