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 Research
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
Changes in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography
Hannestad JO, Cosgrove KP, DellaGioia NF, Perkins E, Bois F, Bhagwagar Z, Seibyl JP, McClure-Begley TD, Picciotto MR, Esterlis I. Changes in the Cholinergic System between Bipolar Depression and Euthymia as Measured with [123I]5IA Single Photon Emission Computed Tomography. Biological Psychiatry 2013, 74: 768-776. PMID: 23773793, PMCID: PMC3805761, DOI: 10.1016/j.biopsych.2013.04.004.Peer-Reviewed Original ResearchConceptsBipolar depressionControl subjectsCholinergic systemSingle photon emissionBipolar disorderAge-matched control subjectsEndogenous acetylcholine levelsNew treatment targetsNicotinic acetylcholine receptorsPhoton emissionLow receptor numbersClinical characteristicsEndogenous acetylcholineDepressive episodeAcetylcholine levelsTomography scanMajor depressionReceptor numberTemporal cortexNAChR numbersTreatment targetsAcetylcholine receptorsControl groupBrain regionsLower β2
2012
Imaging Changes in Synaptic Acetylcholine Availability in Living Human Subjects
Esterlis I, Hannestad JO, Bois F, Sewell RA, Tyndale RF, Seibyl JP, Picciotto MR, Laruelle M, Carson RE, Cosgrove KP. Imaging Changes in Synaptic Acetylcholine Availability in Living Human Subjects. Journal Of Nuclear Medicine 2012, 54: 78-82. PMID: 23160789, PMCID: PMC3703589, DOI: 10.2967/jnumed.112.111922.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptor availabilityEndogenous neurotransmitter acetylcholineNicotinic acetylcholine receptorsPhysostigmine administrationAcetylcholine availabilityExtracellular acetylcholineBaseline scanHealthy subjectsReceptor availabilityExtracellular levelsAcetylcholine receptorsMolecular neuroimagingSPECT studiesAcetylcholineNonhuman primatesTissue concentrationsNeurotransmitter acetylcholineHuman subjectsSignificant reductionAdditional scansScansParent concentrationsSubjectsVivo estimationIASex 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
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 differencesRare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence
Xie P, Kranzler HR, Krauthammer M, Cosgrove KP, Oslin D, Anton RF, Farrer LA, Picciotto MR, Krystal JH, Zhao H, Gelernter J. Rare Nonsynonymous Variants in Alpha-4 Nicotinic Acetylcholine Receptor Gene Protect Against Nicotine Dependence. Biological Psychiatry 2011, 70: 528-536. PMID: 21683344, PMCID: PMC3199609, DOI: 10.1016/j.biopsych.2011.04.017.Peer-Reviewed Original ResearchDissociation 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
2006
Human Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers
Staley JK, Krishnan-Sarin S, Cosgrove KP, Krantzler E, Frohlich E, Perry E, Dubin JA, Estok K, Brenner E, Baldwin RM, Tamagnan GD, Seibyl JP, Jatlow P, Picciotto MR, London ED, O'Malley S, van Dyck CH. Human Tobacco Smokers in Early Abstinence Have Higher Levels of β2* Nicotinic Acetylcholine Receptors than Nonsmokers. Journal Of Neuroscience 2006, 26: 8707-8714. PMID: 16928859, PMCID: PMC6674379, DOI: 10.1523/jneurosci.0546-06.2006.Peer-Reviewed Original ResearchConceptsNAChR availabilityNicotinic acetylcholine receptorsEarly abstinenceAbstinent smokersHuman smokersAcetylcholine receptorsExpired carbon monoxide levelsAbility of smokersHuman tobacco smokersProperties of nicotineSingle photon emissionIA-85380Agonist radiotracerUrinary cotinineTobacco smokingTobacco smokersCerebral cortexLast cigaretteNicotine withdrawalWithdrawal symptomsPrevalent subtypeTobacco smokeAddictive chemicalNicotine dependenceSmokers
2002
Characterization of [125I]epibatidine binding and nicotinic agonist‐mediated 86Rb+ efflux in interpeduncular nucleus and inferior colliculus of β2 null mutant mice
Marks MJ, Whiteaker P, Grady SR, Picciotto MR, McIntosh JM, Collins AC. Characterization of [125I]epibatidine binding and nicotinic agonist‐mediated 86Rb+ efflux in interpeduncular nucleus and inferior colliculus of β2 null mutant mice. Journal Of Neurochemistry 2002, 81: 1102-1115. PMID: 12065623, DOI: 10.1046/j.1471-4159.2002.00910.x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAlkaloidsAnimalsAzocinesBinding, CompetitiveBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugInferior ColliculiIodine RadioisotopesMesencephalonMiceMice, Mutant StrainsNicotinic AgonistsNicotinic AntagonistsPyridinesQuinolizinesReceptors, NicotinicRubidium RadioisotopesTritiumConceptsInterpeduncular nucleusInferior colliculusBrain regionsAccessory olfactory nucleusNull mutant miceOlfactory nucleusNicotinic antagonistsD-tubocurarineMedial habenulaSelective antagonistNicotinic agonistsSuperior colliculusMouse brainAgonistsColliculusMutant micePotent agonistSimilar potencyAntagonistNicotinic activityEfflux
2000
Nicotinic-agonist stimulated 86Rb+ efflux and [3H]epibatidine binding of mice differing in β2 genotype
Marks M, Stitzel J, Grady S, Picciotto M, Changeux J, Collins A. Nicotinic-agonist stimulated 86Rb+ efflux and [3H]epibatidine binding of mice differing in β2 genotype. Neuropharmacology 2000, 39: 2632-2645. PMID: 11044733, DOI: 10.1016/s0028-3908(00)00115-5.Peer-Reviewed Original ResearchConceptsBrain regionsNicotinic acetylcholine receptor functionBeta2 subunitBeta2-containing receptorsAcetylcholine receptor functionHigh-affinity siteBeta2 subunit expressionBinding of mouseCerebral cortexNicotinic responsesMicroM nicotineOlfactory bulbInferior colliculusNicotinic agonistsSubunit expressionReceptor functionLow affinityLow affinity sitesDHbetaEInhibitionMiceStimulationEffluxCytisineNull mutationPharmacological and null mutation approaches reveal nicotinic receptor diversity
Whiteaker P, Marks M, Grady S, Lu Y, Picciotto M, Changeux J, Collins A. Pharmacological and null mutation approaches reveal nicotinic receptor diversity. European Journal Of Pharmacology 2000, 393: 123-135. PMID: 10771005, DOI: 10.1016/s0014-2999(00)00052-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNicotinic acetylcholine receptor functionNicotinic acetylcholine receptorsAcetylcholine receptor functionAcetylcholine receptorsNicotinic acetylcholine receptor bindingReceptor functionNative nicotinic acetylcholine receptorsNicotinic acetylcholine receptor subtypesWhole brain preparationAcetylcholine receptor bindingAcetylcholine receptor subtypesMouse brain membranesArray of assaysReceptor subtypesPharmacological comparisonComparative pharmacologyBrain nucleiBrain membranesEfflux techniqueReceptor bindingSubunit deletionReceptor diversityReceptorsAminobutyric acidSubtypes