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
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