2023
Pathophysiology 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
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 channelsReceptors
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
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 statesReceptorsDisordersNAChRsNicotineMood
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 differencesDissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380
Caldarone BJ, Wang D, Paterson NE, Manzano M, Fedolak A, Cavino K, Kwan M, Hanania T, Chellappan SK, Kozikowski AP, Olivier B, Picciotto MR, Ghavami A. Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380. Psychopharmacology 2011, 217: 199-210. PMID: 21487659, PMCID: PMC3266849, DOI: 10.1007/s00213-011-2271-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntidepressive AgentsAzetidinesBehavior, AnimalBenzazepinesBrainData Interpretation, StatisticalDose-Response Relationship, DrugLigandsMaleMiceMice, Inbred BALB CMice, Inbred C57BLMolecular StructureMotor ActivityNicotinic AgonistsProtein BindingPyridinesQuinoxalinesReceptors, NicotinicSwimmingTime FactorsVareniclineConceptsAntidepressant-like effectsAntidepressant-like actionSwim testDuration of actionReceptor occupancyNAChR antagonist mecamylamineDihydro-β-erythroidineAcetylcholine receptor agonistRole of β2Partial agonist vareniclineSymptoms of depressionNAChR β2Antagonist mecamylamineReceptor agonistActive dosesAgonist vareniclineSazetidinePartial agonistVareniclineObjectivesThe studyBehavioral efficacyNAChRsBehavioral responsesAgonistsPromising target
2010
Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler
Esterlis I, Mitsis EM, Batis JC, Bois F, Picciotto MR, Stiklus SM, Kloczynski T, Perry E, Seibyl JP, McKee S, Staley JK, Cosgrove KP. Brain β2*-nicotinic acetylcholine receptor occupancy after use of a nicotine inhaler. The International Journal Of Neuropsychopharmacology 2010, 14: 389-398. PMID: 21029513, PMCID: PMC3510008, DOI: 10.1017/s1461145710001227.Peer-Reviewed Original ResearchConceptsNicotine inhalerWithdrawal symptomsReceptor occupancyTobacco smokingLow nicotine cigarettesAdministration of nicotineHigh receptor occupancyDoses of nicotineNicotinic acetylcholine receptorsInhaler useTobacco smokersBaseline scanRegular cigarettesInhalerConstant infusionAcetylcholine receptorsSPECT studiesCigarettesSymptomsBeta 2Significant decreaseNicotineSignificant differencesSmokingNAChRsNicotine 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 individualsAcetylcholineReceptorsModulation of ethanol consumption by genetic and pharmacological manipulation of nicotinic acetylcholine receptors in mice
Kamens HM, Andersen J, Picciotto MR. Modulation of ethanol consumption by genetic and pharmacological manipulation of nicotinic acetylcholine receptors in mice. Psychopharmacology 2010, 208: 613-626. PMID: 20072781, PMCID: PMC2901400, DOI: 10.1007/s00213-009-1759-1.Peer-Reviewed Original ResearchConceptsEffects of vareniclineEthanol consumptionNicotinic acetylcholine receptorsEthanol intakeAcetylcholine receptorsPharmacological manipulationΒ2 subunitRole of nAChRsTwo-bottle choice paradigmWild-type micePartial agonist vareniclineSubunit knockout miceMesolimbic dopamine systemNicotinic controlVarenicline doseAlcohol drinkingAgonist vareniclineKnockout miceDopamine systemNicotine responseChallenge studiesVareniclineNAChRsReceptor subunitsMice
2008
Neuroprotection via nAChRs: the role of nAChRs in neurodegenerative disorders such as Alzheimer's and Parkinson's disease.
Picciotto MR, Zoli M. Neuroprotection via nAChRs: the role of nAChRs in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Frontiers In Bioscience-Landmark 2008, 13: 492-504. PMID: 17981563, DOI: 10.2741/2695.Peer-Reviewed Original ResearchConceptsAbility of nicotineNeurodegenerative disordersRole of nAChRsHuman neurodegenerationNeuroprotective agentsParkinson's diseaseDevelopmental stagesCellular effectsNicotine-mediated neuroprotectionRegimen of administrationDrug discoveryNicotine neuroprotectionNeuronal survivalNeuronal deathEpidemiological studiesNicotinic compoundsAlzheimer's diseaseRecent studiesNeuroprotectionDiseaseNicotineCompelling evidenceNAChRsVivoFull understanding
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 effectsNAChRsDesensitization
2006
The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo
Miwa JM, Stevens TR, King SL, Caldarone BJ, Ibanez-Tallon I, Xiao C, Fitzsimonds RM, Pavlides C, Lester HA, Picciotto MR, Heintz N. The Prototoxin lynx1 Acts on Nicotinic Acetylcholine Receptors to Balance Neuronal Activity and Survival In Vivo. Neuron 2006, 51: 587-600. PMID: 16950157, DOI: 10.1016/j.neuron.2006.07.025.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAge FactorsAnimalsAssociation LearningBrainCell SurvivalExcitatory Amino Acid AgonistsMembrane GlycoproteinsMembrane PotentialsMiceMice, Mutant StrainsMutationNerve DegenerationNeuronsNeuropeptidesNicotineNicotinic AgonistsPatch-Clamp TechniquesReceptors, NicotinicConceptsNicotinic acetylcholine receptorsNull mutant miceMutant miceAcetylcholine receptorsNeuronal activityNull mutationBiological processesLynx1Calcium levelsAgonist sensitivityReceptor desensitizationSynaptic efficacyMutationsAllosteric modulatorsDesensitization kineticsWide arrayNicotineVivoSpecific testsNAChRsMiceReceptorsSurvivalHyperactivationFunction
2002
Effect of nicotine and nicotinic receptors on anxiety and depression
Picciotto MR, Brunzell DH, Caldarone BJ. Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport 2002, 13: 1097-1106. PMID: 12151749, DOI: 10.1097/00001756-200207020-00006.Peer-Reviewed Original ResearchConceptsNicotine treatmentActivation of nAChRsDorsal raphe nucleusEffects of nicotineMesolimbic dopamine systemNicotinic acetylcholine receptorsNicotine administrationMonoaminergic transmissionChronic useRaphe nucleusAnxiolytic actionLateral septumNicotinic receptorsClassical neurotransmittersNormal brainAnimal studiesDopamine systemBrain areasAcetylcholine receptorsNicotineEnsemble of studiesNAChRsAnxiety modelsAdministration studiesDepression
2001
Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications
Picciotto M, Caldarone B, Brunzell D, Zachariou V, Stevens T, King S. Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications. Pharmacology & Therapeutics 2001, 92: 89-108. PMID: 11916531, DOI: 10.1016/s0163-7258(01)00161-9.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSignal transduction pathwaysHomologous recombinationTransduction pathwaysGenetic manipulationMolecular basisBehavioral phenotypesInactivation of nAChRsNicotinic acetylcholine receptorsSubunit compositionSubunitsNeuronal nicotinic receptorsPersistent activationNeurotransmitter releaseRelevant mutationsModel systemPossible clinical implicationsPhysiological propertiesAcetylcholine receptorsPhenotypeAutonomic gangliaNicotinic receptorsDisease statesDrug developmentPharmacological actionsNAChRs
2000
5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors
Mukhin A, Gündisch D, Horti A, Koren A, Tamagnan G, Kimes A, Chambers J, Vaupel D, King S, Picciotto M, Innis R, London E. 5-Iodo-A-85380, an α4β2 Subtype-Selective Ligand for Nicotinic Acetylcholine Receptors. Molecular Pharmacology 2000, 57: 642-649. PMID: 10692507, DOI: 10.1124/mol.57.3.642.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAlpha4beta2 nAChRsAcetylcholine receptorsNeuronal nicotinic acetylcholine receptorsAffinity of epibatidineRat adrenal glandMuscle-type nAChRsSubtype-selective ligandsAlpha4beta2 subtypeAdrenal glandRat brainSelective radioligandBrain regionsNAChRsBeta4 subunitsRadioiodinated ligandBeta2 subunitVivo studiesEpibatidineVivo experimentsHuman brainSubtypesRadioligandBrainReceptors