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 receptors
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
Sex differences in amphetamine-induced dopamine release in the dorsolateral prefrontal cortex of tobacco smokers
Zakiniaeiz Y, Hillmer AT, Matuskey D, Nabulsi N, Ropchan J, Mazure CM, Picciotto MR, Huang Y, McKee SA, Morris ED, Cosgrove KP. Sex differences in amphetamine-induced dopamine release in the dorsolateral prefrontal cortex of tobacco smokers. Neuropsychopharmacology 2019, 44: 2205-2211. PMID: 31269510, PMCID: PMC6897943, DOI: 10.1038/s41386-019-0456-y.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDA releasePositron emission tomographyD2R availabilityDorsolateral prefrontal cortexMale smokersFemale smokersTobacco smokingPrefrontal cortexAmphetamine-induced DA releaseAmphetamine-induced dopamine releaseCortical DA releaseMesocortical DA systemEffects of nicotineSmoking-related behaviorsMesolimbic dopamine systemLong-term abstinenceSex differencesGender-specific treatmentFemale nonsmokersTobacco smokersAmphetamine administrationDopamine releaseNeurochemical mechanismsNonsmokersSmokers
2015
Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress
Mineur YS, Fote GM, Blakeman S, Cahuzac EL, Newbold SA, Picciotto MR. Multiple Nicotinic Acetylcholine Receptor Subtypes in the Mouse Amygdala Regulate Affective Behaviors and Response to Social Stress. Neuropsychopharmacology 2015, 41: 1579-1587. PMID: 26471256, PMCID: PMC4832019, DOI: 10.1038/npp.2015.316.Peer-Reviewed Original ResearchConceptsDepression-like behaviorBasolateral amygdalaΑ7 nAChRsCholinergic signalingMultiple nicotinic acetylcholine receptor subtypesNon-selective nAChR antagonist mecamylamineNicotinic acetylcholine receptor activityNicotinic acetylcholine receptor subtypesStress-mediated behaviorsAntidepressant-like effectsAcetylcholine receptor activityC-Fos immunoreactivityNAChR antagonist mecamylamineAcetylcholine receptor subtypesEffects of nicotineMajor depressive disorderSocial defeat stressAnxiety-like behaviorPre-clinical studiesHuman clinical trialsModels of anxietyMouse behavioral modelsHypercholinergic stateAntagonist mecamylamineLocal infusionMood 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
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 studiesNicotineMetabolismMammalsSex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers
Cosgrove KP, Esterlis I, McKee SA, Bois F, Seibyl JP, Mazure CM, Krishnan-Sarin S, Staley JK, Picciotto MR, O’Malley S. Sex Differences in Availability of β2*-Nicotinic Acetylcholine Receptors in Recently Abstinent Tobacco Smokers. JAMA Psychiatry 2012, 69: 418-427. PMID: 22474108, PMCID: PMC3508698, DOI: 10.1001/archgenpsychiatry.2011.1465.Peer-Reviewed Original ResearchMeSH KeywordsAdultAzetidinesBehavior, AddictiveBrainDepressionEstradiolFemaleFunctional NeuroimagingHumansIodine RadioisotopesMaleNicotinic AntagonistsProgesteronePyridinesRadioligand AssayReceptors, NicotinicSex CharacteristicsSmokingSubstance Withdrawal SyndromeTomography, Emission-Computed, Single-PhotonConceptsNAChR availabilityFemale smokersTobacco smokersNicotinic acetylcholine receptorsFemale nonsmokersProgesterone levelsAcetylcholine receptorsFemale sex steroid hormonesSex differencesSex steroid hormone levelsAbstinent tobacco smokersSex-matched nonsmokersTobacco smoking effectsMagnetic resonance imaging studyAge-matched malesEquilibrium distribution volumeEffects of nicotineSex steroid hormonesSteroid hormone levelsUnderlying neurochemical mechanismsResonance imaging studySingle photon emissionDays of abstinenceIA SPECTNicotine therapy
2010
Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference
Neugebauer NM, Henehan RM, Hales CA, Picciotto MR. Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference. Pharmacology Biochemistry And Behavior 2010, 98: 87-93. PMID: 21172385, PMCID: PMC3030658, DOI: 10.1016/j.pbb.2010.12.015.Peer-Reviewed Original ResearchConceptsGal-/- miceAcute nicotine administrationNicotine CPPPlace preferenceNicotine administrationRewarding effectsRole of galaninEffects of nicotineNucleus accumbens shellClass of drugsAmphetamine place preferenceDrugs of abuseGalanin signalingNeuropeptide galaninCPP chamberAlcohol drinkingNicotine rewardSignificant CPPExtracellular signal-related kinaseAccumbens shellGalanin peptideHigh doseSystem activationAlcohol preferenceSignal-related kinaseNicotine 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
2008
Role of β2-containing nicotinic acetylcholine receptors in auditory event-related potentials
Rudnick ND, Koehler C, Picciotto MR, Siegel SJ. Role of β2-containing nicotinic acetylcholine receptors in auditory event-related potentials. Psychopharmacology 2008, 202: 745-751. PMID: 18931833, DOI: 10.1007/s00213-008-1358-6.Peer-Reviewed Original ResearchConceptsAuditory event-related potentialsEffects of nicotineWild-type miceN40 amplitudeNicotine effectsSpecific nicotinic acetylcholine receptor subtypesNicotinic acetylcholine receptor subtypesΒ2-containing receptorsAcetylcholine receptor subtypesEvent-related potentialsSensory processingΒ2 knockout miceSchizophrenic individualsNicotinic acetylcholine receptorsModulates sensory processingAuditory ERP responsesNicotine administrationReceptor subtypesCA3 regionKnockout miceTherapeutic targetClick stimuliN40 componentStereotaxic implantationAcetylcholine receptorsAntidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression
Vieyra-Reyes P, Mineur YS, Picciotto MR, Túnez I, Vidaltamayo R, Drucker-Colín R. Antidepressant-like effects of nicotine and transcranial magnetic stimulation in the olfactory bulbectomy rat model of depression. Brain Research Bulletin 2008, 77: 13-18. PMID: 18582540, PMCID: PMC2771408, DOI: 10.1016/j.brainresbull.2008.05.007.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsBehavior, AnimalDepressionDisease Models, AnimalDrug Administration ScheduleExploratory BehaviorInjections, IntraperitonealMaleMotor ActivityNicotineOlfactory BulbPsychology, ComparativeRatsRats, Long-EvansRats, WistarSelf AdministrationSpecies SpecificitySwimmingTranscranial Magnetic StimulationConceptsDepression-like symptomsTranscranial magnetic stimulationAntidepressant-like effectsWistar ratsMagnetic stimulationOlfactory bulbectomyRat strainsDaily transcranial magnetic stimulationOlfactory bulbectomy rat modelEffects of nicotineOral nicotine intakeOral intakeDepression managementSwim testTherapeutic alternativeNicotine intakeRat modelLong-Evans rat strainDepression susceptibilitySymptomsLong-EvansNicotineInnate differencesRatsBulbectomy
2007
It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood
Picciotto MR, Addy NA, Mineur YS, Brunzell DH. It is not “either/or”: Activation and desensitization of nicotinic acetylcholine receptors both contribute to behaviors related to nicotine addiction and mood. Progress In Neurobiology 2007, 84: 329-342. PMID: 18242816, PMCID: PMC2390914, DOI: 10.1016/j.pneurobio.2007.12.005.Peer-Reviewed Original ResearchConceptsDesensitization of nAChRsNicotinic acetylcholine receptorsNicotine addictionDrug reinforcementAcetylcholine receptorsAntidepressant-like effectsActivation of nAChRsEffects of nicotineNicotine-mediated behaviorsRecent electrophysiological studiesNicotine administrationTobacco smokingAffective modulationNicotine resultsElectrophysiological studiesSmoking behaviorNicotinic agentsReceptor desensitizationDrug rewardBehavioral consequencesAffective behaviorBehavioral processesBehavioral effectsNAChRsDesensitizationRole of Calcineurin in Nicotine-Mediated Locomotor Sensitization
Addy NA, Fornasiero EF, Stevens TR, Taylor JR, Picciotto MR. Role of Calcineurin in Nicotine-Mediated Locomotor Sensitization. Journal Of Neuroscience 2007, 27: 8571-8580. PMID: 17687035, PMCID: PMC6672935, DOI: 10.1523/jneurosci.2601-07.2007.Peer-Reviewed Original ResearchConceptsVentral tegmental areaEffects of nicotineLocomotor sensitizationCalcineurin inhibitorsRole of calcineurinInfusion of rapamycinCultured cortical neuronsSprague-Dawley ratsNicotine-mediated behaviorsCyclosporine administrationTegmental areaCortical neuronsDawley ratsFK-binding proteinActivation of calcineurinNicotineSensitizationCalcineurin activityInfusionIntracellular signalingAdministrationCalcineurinFK506InhibitorsDirect infusion
2005
β2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice
Brunzell DH, Chang JR, Schneider B, Olausson P, Taylor JR, Picciotto MR. β2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice. Psychopharmacology 2005, 184: 328-338. PMID: 16133126, DOI: 10.1007/s00213-005-0099-z.Peer-Reviewed Original ResearchConceptsNicotine exposureNicotinic acetylcholine receptorsFood-reinforced respondingAcetylcholine receptorsPrior nicotine exposureNicotine-induced increasesProgressive ratioNicotinic receptor subtypesEffects of nicotineWild-type miceProgressive ratio testC57BL/6 miceReceptor subtypesConclusionThese dataChronic exposureReinforcement testingMiceΒ2 subunitUnpaired presentationsExposureReceptorsApproach trainingPresentationPaired presentationsPrimary reinforcement
2004
Role of neuronal nicotinic receptors in the effects of nicotine and ethanol on contextual fear conditioning
Wehner JM, Keller JJ, Keller AB, Picciotto MR, Paylor R, Booker TK, Beaudet A, Heinemann SF, Balogh SA. Role of neuronal nicotinic receptors in the effects of nicotine and ethanol on contextual fear conditioning. Neuroscience 2004, 129: 11-24. PMID: 15489024, DOI: 10.1016/j.neuroscience.2004.07.016.Peer-Reviewed Original ResearchConceptsContextual learningForms of learningEffects of nicotineFear conditioningCued fear conditioningContextual fear conditioningCognitive enhancing effectsBeta2 null mutant miceNicotine effectsBeta4-containing receptorsShock stimuliEffects of ethanolBeta2-containing nAChRsLearningNull mutant miceTrainingConditioningBrain nicotinic acetylcholine receptorsMutant miceNicotineNeuronal nicotinic receptorsHomozygous null mutant miceWild-type littermatesMemoryNicotinic acetylcholine receptors
2003
Neuroprotection by Nicotine in Mouse Primary Cortical Cultures Involves Activation of Calcineurin and L-Type Calcium Channel Inactivation
Stevens TR, Krueger SR, Fitzsimonds RM, Picciotto MR. Neuroprotection by Nicotine in Mouse Primary Cortical Cultures Involves Activation of Calcineurin and L-Type Calcium Channel Inactivation. Journal Of Neuroscience 2003, 23: 10093-10099. PMID: 14602824, PMCID: PMC6740855, DOI: 10.1523/jneurosci.23-31-10093.2003.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBungarotoxinsCalcineurinCalcineurin InhibitorsCalcium Channel BlockersCalcium Channels, L-TypeCells, CulturedCerebral CortexGlutamic AcidMiceMice, KnockoutNeuronsNeuroprotective AgentsNeurotoxinsNicotineNifedipineReceptors, NicotinicTacrolimusConceptsPrimary cortical culturesL-type channelsNicotine-mediated neuroprotectionCortical culturesNicotine pretreatmentIntracellular calciumCalcium influxActivation of calcineurinBeta2 subunitAlpha7-containing nAChRsL-type calcium channelsEffects of nicotineAbility of nicotineMouse primary cortical culturesNicotinic acetylcholine receptorsCalcium channel inactivationGlutamate excitotoxicityNeuroprotective effectsRole of calciumCalcineurin antagonistsCortical neuronsNeuronal excitabilityGlutamate applicationNeuroprotectionCalcium channelsNicotine 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 behaviorSmokingPathwaySubtypesReceptorsConditional Expression in Corticothalamic Efferents Reveals a Developmental Role for Nicotinic Acetylcholine Receptors in Modulation of Passive Avoidance Behavior
King SL, Marks MJ, Grady SR, Caldarone BJ, Koren AO, Mukhin AG, Collins AC, Picciotto MR. Conditional Expression in Corticothalamic Efferents Reveals a Developmental Role for Nicotinic Acetylcholine Receptors in Modulation of Passive Avoidance Behavior. Journal Of Neuroscience 2003, 23: 3837-3843. PMID: 12736354, PMCID: PMC6742204, DOI: 10.1523/jneurosci.23-09-03837.2003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAvoidance LearningBehavior, AnimalBinding, CompetitiveCerebral CortexElectroshockGene Expression Regulation, DevelopmentalMiceMice, Inbred C57BLMice, Inbred ICRMice, KnockoutMice, TransgenicNeurons, EfferentNicotineNicotinic AgonistsPresynaptic TerminalsReceptors, NicotinicTetracyclineThalamusTransgenesConceptsPrenatal nicotine exposureNicotinic acetylcholine receptorsPassive avoidanceLines of miceNicotine exposureTransgenic miceAcetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsTetracycline-regulated transgenic systemHigh-affinity nicotinic receptorsPotential neuroanatomical substratesRubidium efflux assaysHigh-affinity nAChRsEffects of nicotineSpecific neuronal populationsPassive avoidance behaviorAttention deficit hyperactivity disorderWild-type animalsDeficit hyperactivity disorderPresynaptic nAChRsCorticothalamic neuronsSite of actionNicotinic receptorsNeuronal populationsCognitive impairment