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
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
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 signalingSmokers
2012
AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors
Dietrich MO, Bober J, Ferreira JG, Tellez LA, Mineur YS, Souza DO, Gao XB, Picciotto MR, Araújo I, Liu ZW, Horvath TL. AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors. Nature Neuroscience 2012, 15: 1108-1110. PMID: 22729177, PMCID: PMC3411867, DOI: 10.1038/nn.3147.Peer-Reviewed Original Research
2011
Reduced locomotor responses to cocaine in ghrelin-deficient mice
Abizaid A, Mineur YS, Roth RH, Elsworth JD, Sleeman MW, Picciotto MR, Horvath TL. Reduced locomotor responses to cocaine in ghrelin-deficient mice. Neuroscience 2011, 192: 500-506. PMID: 21699961, DOI: 10.1016/j.neuroscience.2011.06.001.Peer-Reviewed Original ResearchConceptsGhrelin KO miceWT miceDopamine releaseLocomotor activityBehavioral effectsDopamine metabolite concentrationsGhrelin-deficient miceLocomotor-stimulating effectsDopamine cell activityEffects of cocaineMesolimbic dopaminergic systemWild-type littermatesOrexigenic hormoneChronic injectionsDopamine utilizationDaily injectionsStriatal dopamineMesolimbic systemWT littermatesDopaminergic systemDaily cocaineFood intakeRewarding effectsPsychostimulant effectsLocomotor response
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
2008
Galanin – 25 years with a multitalented neuropeptide
Picciotto MR. Galanin – 25 years with a multitalented neuropeptide. Cellular And Molecular Life Sciences 2008, 65: 1872-1879. PMID: 18500649, PMCID: PMC11131873, DOI: 10.1007/s00018-008-8151-x.Peer-Reviewed Original ResearchConceptsGalanin receptorsFood intakeOpiate rewardDrug rewardGalanin – 25 yearsAbility of neuropeptidesMesolimbic dopamine systemDrugs of abuseGalanin agonistsNoradrenergic neuronsDrug withdrawalStriatal slicesWithdrawal signsAnalgesic propertiesLocus coeruleusHypothalamic functionDopamine releaseDopamine systemGalaninNovel treatmentsPlace preferenceStress-related pathwaysFiring ratePotential targetWithdrawal
2007
Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons
Rao Y, Liu ZW, Borok E, Rabenstein RL, Shanabrough M, Lu M, Picciotto MR, Horvath TL, Gao XB. Prolonged wakefulness induces experience-dependent synaptic plasticity in mouse hypocretin/orexin neurons. Journal Of Clinical Investigation 2007, 117: 4022-4033. PMID: 18060037, PMCID: PMC2104495, DOI: 10.1172/jci32829.Peer-Reviewed Original ResearchConceptsHypocretin/orexin neuronsLong-term potentiationOrexin neuronsGlutamatergic synapsesSynaptic plasticitySleep lossExperience-dependent synaptic plasticityDopamine D1 receptorsChronic sleep lossSleep-wake regulationModafinil treatmentLateral hypothalamusD1 receptorsSimilar potentiationBrain slicesNeuronal activityNeuronal circuitryDopamine systemNervous systemSynaptic strengthNeuronsPathological conditionsGentle handlingMiceWakefulness
2006
Differential effects of nicotinic antagonists perfused into the nucleus accumbens or the ventral tegmental area on cocaine-induced dopamine release in the nucleus accumbens of mice
Zanetti L, Picciotto MR, Zoli M. Differential effects of nicotinic antagonists perfused into the nucleus accumbens or the ventral tegmental area on cocaine-induced dopamine release in the nucleus accumbens of mice. Psychopharmacology 2006, 190: 189. PMID: 17061109, DOI: 10.1007/s00213-006-0598-6.Peer-Reviewed Original ResearchConceptsIntra-VTA perfusionVentral tegmental areaDA levelsNucleus accumbensCocaine-elicited increasesPerfusate levelsTegmental areaCocaine-induced dopamine releaseNicotinic acetylcholine receptor antagonistMesolimbic DA neuronsDihydro-β-erythroidineAcetylcholine receptor antagonistEffects of cocaineMesolimbic dopamine systemSubtype-specific mannerDA neuronsNAChR antagonistIntracerebral microdialysisNicotinic antagonistsReceptor antagonistNicotinic pathwayLocal perfusionDopamine releaseDopamine systemPerfusionGhrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite
Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, Horvath TL. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. Journal Of Clinical Investigation 2006, 116: 3229-3239. PMID: 17060947, PMCID: PMC1618869, DOI: 10.1172/jci29867.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsAppetiteDopamineFluorescent Antibody TechniqueGhrelinMaleMesencephalonMiceMice, Inbred C57BLMice, KnockoutNeuronsNucleus AccumbensPatch-Clamp TechniquesPeptide HormonesRatsRats, Sprague-DawleyReceptors, GhrelinReceptors, G-Protein-CoupledTime FactorsVentral Tegmental AreaConceptsVentral tegmental areaGHSR-deficient miceGHSR-dependent mannerGut hormone ghrelinDopamine neuronal activityMidbrain dopamine neuronsMesolimbic reward circuitrySynaptic input organizationPeripheral ghrelinRebound feedingVTA administrationOrexigenic effectDopamine turnoverGHSR antagonistDopamine neuronsHypothalamic centersTegmental areaHormone ghrelinNucleus accumbensGhrelinNeuronal activitySynapse formationReward circuitryInput organizationFeeding scheduleInhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum
Zanetti L, de Kerchove D’Exaerde A, Zanardi A, Changeux JP, Picciotto MR, Zoli M. Inhibition of both α7* and β2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum. Psychopharmacology 2006, 187: 181-188. PMID: 16826402, DOI: 10.1007/s00213-006-0419-y.Peer-Reviewed Original ResearchConceptsExtracellular dopamine levelsDevelopment of sensitizationWild-type miceDopamine levelsVentral striatumCocaine-elicited increasesExtracellular DA levelsAdministration of cocaineDihydro-β-erythroidineAbility of cocaineNicotinic acetylcholine receptorsNicotine treatmentDA levelsNicotinic antagonistsRationaleSeveral studiesNeurochemical responsesConclusionsThese dataObjectivesThe current studySpecific antagonistNAChR blockadeAcetylcholine receptorsElicit increasesStriatumMiceSensitization
2004
β2-subunit-containing nicotinic acetylcholine receptors are critical for dopamine-dependent locomotor activation following repeated nicotine administration
King SL, Caldarone BJ, Picciotto MR. β2-subunit-containing nicotinic acetylcholine receptors are critical for dopamine-dependent locomotor activation following repeated nicotine administration. Neuropharmacology 2004, 47: 132-139. PMID: 15464132, DOI: 10.1016/j.neuropharm.2004.06.024.Peer-Reviewed Original ResearchConceptsLocomotor activationNicotine administrationDopamine systemNicotinic acetylcholine receptorsAcetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsDopamine receptor antagonist pimozideBeta2 subunitRole of beta2Chronic nicotine administrationChronic nicotine exposureMesolimbic dopamine systemChronic nicotineNicotine exposureAntagonist pimozideB6 miceC57BL/6J miceOral administrationDopaminergic activationOngoing activationKnockout miceLocomotor activityMiceAdministrationNicotine
2002
Acute and long‐term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections
Ferrari R, Le Novère N, Picciotto MR, Changeux JP, Zoli M. Acute and long‐term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections. European Journal Of Neuroscience 2002, 15: 1810-1818. PMID: 12081661, DOI: 10.1046/j.1460-9568.2001.02009.x.Peer-Reviewed Original ResearchMeSH KeywordsAmphetamineAnimalsDopamineDopamine Plasma Membrane Transport ProteinsDrug Administration RoutesExtracellular SpaceHabituation, PsychophysiologicMaleMembrane GlycoproteinsMembrane Transport ProteinsMicrodialysisMotor ActivityNerve Tissue ProteinsNeural PathwaysNeuronal PlasticityNicotineNucleus AccumbensPresynaptic TerminalsRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateRNA, MessengerSubstance-Related DisordersTime FactorsTyrosine 3-MonooxygenaseVentral Tegmental AreaConceptsDialysate DA levelsGluR1 mRNA levelsSingle nicotine injectionNicotine administrationDA levelsMesolimbic dopamine pathwayNicotine injectionTyrosine hydroxylaseDopamine pathwayMRNA levelsBasal DA levelsExtracellular DA levelsMesolimbic DA pathwaySystemic intraperitoneal injectionTH mRNA levelsIntra-accumbens infusionReduction of cocaine place preference in mice lacking the protein phosphatase 1 inhibitors DARPP 32 or Inhibitor 1
Zachariou V, Benoit-Marand M, Allen PB, Ingrassia P, Fienberg AA, Gonon F, Greengard P, Picciotto MR. Reduction of cocaine place preference in mice lacking the protein phosphatase 1 inhibitors DARPP 32 or Inhibitor 1. Biological Psychiatry 2002, 51: 612-620. PMID: 11955461, DOI: 10.1016/s0006-3223(01)01318-x.Peer-Reviewed Original ResearchAnimalsAvoidance LearningBehavior, AnimalCocaineCorpus StriatumDopamineDopamine and cAMP-Regulated Phosphoprotein 32Dopamine Uptake InhibitorsElectric StimulationElectrochemistryMaleMiceMice, KnockoutMotor ActivityNerve Tissue ProteinsPhosphoprotein PhosphatasesPhosphoproteinsProtein Phosphatase 1Proteins
2001
Nicotine Receptor Inactivation Decreases Sensitivity to Cocaine
Zachariou V, Caldarone B, Weathers-Lowin A, George T, Elsworth J, Roth R, Changeux J, Picciotto M. Nicotine Receptor Inactivation Decreases Sensitivity to Cocaine. Neuropsychopharmacology 2001, 24: 576-589. PMID: 11282258, DOI: 10.1016/s0893-133x(00)00224-4.Peer-Reviewed Original ResearchConceptsPlace preferenceDA turnoverLow doseHigh-affinity nicotinic acetylcholine receptorsMesolimbic DA systemHigh-affinity nAChRsNicotinic antagonist mecamylamineWild-type miceMesolimbic dopamine systemFos-related antigensProperties of nicotineCocaine place preferenceΒ2 subunitNicotinic acetylcholine receptorsAntagonist mecamylamineDA releaseMetabolite DOPACNeurochemical changesSubthreshold doseType miceDopamine systemPsychomotor stimulantsAcetylcholine receptorsHigh dosesBrain regionsEffects of nicotine pretreatment on dopaminergic and behavioral responses to conditioned fear stress in rats: dissociation of biochemical and behavioral effects
George T, Picciotto M, Verrico C, Roth R. Effects of nicotine pretreatment on dopaminergic and behavioral responses to conditioned fear stress in rats: dissociation of biochemical and behavioral effects. Biological Psychiatry 2001, 49: 300-306. PMID: 11230881, DOI: 10.1016/s0006-3223(00)00928-8.Peer-Reviewed Original ResearchConceptsConditioned fear stressNicotine pretreatmentMedial prefrontal cortexFear stressDopamine metabolismNucleus accumbensPrefrontal cortexAcute footshock stressImmobility responseBehavioral responsesCortical dopaminergicDopamine utilizationCortical dopamineNicotine exposureFootshock stressNicotine dependenceAnxiolytic activityConditioned fear paradigmNicotine differsDay 21Psychological stressorsBehavioral effectsDopaminergicClinical contextPreferential activationNicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum
Grady S, Meinerz N, Cao J, Reynolds A, Picciotto M, Changeux J, McIntosh J, Marks M, Collins A. Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum. Journal Of Neurochemistry 2001, 76: 258-268. PMID: 11145999, DOI: 10.1046/j.1471-4159.2001.00019.x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAlkaloidsAnimalsAzocinesCalciumCholineConotoxinsCorpus StriatumDopamineDose-Response Relationship, DrugFemaleHeterozygoteHomozygoteMaleMesencephalonMiceMice, Inbred C57BLMice, Mutant StrainsNicotinic AgonistsNicotinic AntagonistsPresynaptic TerminalsProtein SubunitsQuinolizinesReceptors, NicotinicSynaptosomesConceptsAgonist-stimulated releaseAcetylcholine releaseInterpeduncular nucleusStriatal synaptosomesDopamine releaseNicotinic agonistsAlpha-conotoxin MIIMouse striatal synaptosomesAlpha-conotoxin AuIBNicotinic acetylcholine receptorsDose-response curveAcetylcholine receptorsExternal calciumDifferent nAChRsDesensitization ratePersistent phaseAgonistsL nicotineSynaptosomesNull mutationSimilar decreaseInhibition curvesMiceReleaseAcetylcholine
2000
Nicotinic modulation of mesoprefrontal dopamine neurons: pharmacologic and neuroanatomic characterization.
George TP, Verrico CD, Picciotto MR, Roth RH. Nicotinic modulation of mesoprefrontal dopamine neurons: pharmacologic and neuroanatomic characterization. Journal Of Pharmacology And Experimental Therapeutics 2000, 295: 58-66. PMID: 10991961.Peer-Reviewed Original ResearchConceptsMesoprefrontal DA neuronsDA neuronsLocal infusionNicotinic acetylcholine receptor stimulationMesoprefrontal dopamine neuronsMesoprefrontal dopamine systemEndogenous opioid peptidesVentral tegmental areaHigh comorbid ratesNicotine-pretreated ratsMedial prefrontal cortexDA metabolismNicotinic modulationCortical dysfunctionNicotine administrationCigarette smokingSite of actionStress-induced statesNicotine pretreatmentDA dysregulationDopamine neuronsSystemic administrationTegmental areaDA dysfunctionCognitive dysfunction
1998
Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine
Picciotto M, Zoli M, Rimondini R, Léna C, Marubio L, Pich E, Fuxe K, Changeux J. Acetylcholine receptors containing the β2 subunit are involved in the reinforcing properties of nicotine. Nature 1998, 391: 173-177. PMID: 9428762, DOI: 10.1038/34413.Peer-Reviewed Original ResearchMeSH Keywords3,4-Dihydroxyphenylacetic AcidAcetylcholineAnimalsBinding SitesCarrier ProteinsCocaineConditioning, OperantDopamineDopamine Plasma Membrane Transport ProteinsHomovanillic AcidIn Vitro TechniquesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiceMice, Inbred C57BLMice, Inbred DBAMice, KnockoutMicrodialysisMotor ActivityNerve Tissue ProteinsNicotineNucleus AccumbensPatch-Clamp TechniquesReceptors, NicotinicSecond Messenger SystemsSubstantia NigraVentral Tegmental AreaConceptsProperties of nicotineAcetylcholine receptorsVentral striatumΒ2 subunitNeuronal nicotinic acetylcholine receptorsMesencephalic dopaminergic neuronsEffects of nicotineWild-type micePatch-clamp recordingsMesolimbic dopamine systemNicotinic acetylcholine receptorsDrugs of abuseDopaminergic neuronsMesolimbic systemDopamine releaseDopamine systemMutant miceMiceNicotineNeurotransmitter dopamineStriatumReceptorsNeuronsReleaseBrain