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 infusionModulation of aggressive behavior in mice by nicotinic receptor subtypes
Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR. Modulation of aggressive behavior in mice by nicotinic receptor subtypes. Biochemical Pharmacology 2015, 97: 488-497. PMID: 26212554, PMCID: PMC4600457, DOI: 10.1016/j.bcp.2015.07.019.Peer-Reviewed Original ResearchConceptsAcute nicotine administrationNicotine administrationHypolocomotor effectNicotinic acetylcholine receptor agonist nicotineAgonist GTS-21Nicotinic receptor subtypesAnti-aggressive propertiesDihydro-β-erythroidineBALB/cNeurobiology of aggressionSocial interaction timeCurrent pharmacotherapyAntagonist methyllycaconitineC57BL/6 miceWorse outcomesGTS-21Receptor subtypesPathological aggressionAgonist nicotineΑ7 nAChRsSpecific treatmentSide effectsPharmacological studiesNeuropsychiatric conditionsNicotine
2012
Sex 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
Plasticity of Prefrontal Attention Circuitry: Upregulated Muscarinic Excitability in Response to Decreased Nicotinic Signaling Following Deletion of α5 or β2 Subunits
Tian MK, Bailey CD, De Biasi M, Picciotto MR, Lambe EK. Plasticity of Prefrontal Attention Circuitry: Upregulated Muscarinic Excitability in Response to Decreased Nicotinic Signaling Following Deletion of α5 or β2 Subunits. Journal Of Neuroscience 2011, 31: 16458-16463. PMID: 22072695, PMCID: PMC3240894, DOI: 10.1523/jneurosci.3600-11.2011.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAge FactorsAnalysis of VarianceAnimalsAtropineDihydro-beta-ErythroidineIntracellular Signaling Peptides and ProteinsMaleMembrane PotentialsMiceMice, KnockoutNeuronal PlasticityNeuronsNeuropeptidesNeurotransmitter AgentsNicotineNicotinic AntagonistsOrexinsPatch-Clamp TechniquesPrefrontal CortexReceptors, MuscarinicReceptors, NicotinicSignal TransductionUp-RegulationConceptsLayer VI neuronsNicotinic receptorsCholinergic excitationCholinergic receptorsPrefrontal cortexExcitatory muscarinic receptorsPrefrontal attention circuitryMuscarinic cholinergic receptorsMuscarinic acetylcholine receptorsAcute brain slicesWild-type miceWhole-cell recordingsΒ2 subunitNicotinic receptor subunitsMedial prefrontal cortexPyramidal neuronsMuscarinic receptorsNicotinic signalingLayer VIAttention circuitryCholinergic stimulationBrain slicesNicotinic stimulationAcetylcholine receptorsTiming of excitationDecreased 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 differencesNociceptive thresholds are controlled through spinal β2-subunit-containing nicotinic acetylcholine receptors
Yalcin I, Charlet A, Cordero-Erausquin M, Tessier L, Picciotto MR, Schlichter R, Poisbeau P, Freund-Mercier M, Barrot M. Nociceptive thresholds are controlled through spinal β2-subunit-containing nicotinic acetylcholine receptors. Pain 2011, 152: 2131-2137. PMID: 21794985, DOI: 10.1016/j.pain.2011.05.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsMaleMiceNicotinic AntagonistsNociceptionPain ThresholdReceptors, NicotinicSpinal CordConceptsNociceptive thresholdKO miceNicotinic acetylcholine receptorsNociceptive informationMechanical thresholdHigh-frequency transcutaneous electrical nerve stimulationAcetylcholine receptorsTranscutaneous electrical nerve stimulationHigh-frequency TENSInhibitory controlReceptor antagonist bicucullineElectrical nerve stimulationC-fiber stimulationTonic inhibitory controlMechanical nociceptive thresholdThermal nociceptive thresholdInhibitory transmissionAntagonist bicucullineGABAergic controlGABAergic transmissionEndogenous acetylcholineGABAergic inhibitionNerve stimulationNociceptive processingNociceptive responses
2010
Nicotine 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
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 systemPerfusionThe nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice
Rabenstein RL, Caldarone BJ, Picciotto MR. The nicotinic antagonist mecamylamine has antidepressant-like effects in wild-type but not β2- or α7-nicotinic acetylcholine receptor subunit knockout mice. Psychopharmacology 2006, 189: 395-401. PMID: 17016705, DOI: 10.1007/s00213-006-0568-z.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsAntagonist mecamylamineNicotinic acetylcholine receptor activityNoncompetitive nAChR antagonist mecamylamineAntagonist dihydro-β-erythroidineΑ7 knockout miceΑ7-nAChR subunitAcetylcholine receptor activityEffects of mecamylamineNAChR antagonist mecamylamineDihydro-β-erythroidineNicotinic antagonist mecamylamineSubunit knockout miceBaseline locomotor activityDose-response studyMethodsAdult miceAntagonist hexamethoniumAntidepressant efficacyAntidepressant responseCentral nAChRsImmobility timeCholinergic transmissionSwim testMecamylamineSuspension testInhibition 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
High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation
Caldarone BJ, Harrist A, Cleary MA, Beech RD, King SL, Picciotto MR. High-affinity nicotinic acetylcholine receptors are required for antidepressant effects of amitriptyline on behavior and hippocampal cell proliferation. Biological Psychiatry 2004, 56: 657-664. PMID: 15522249, DOI: 10.1016/j.biopsych.2004.08.010.Peer-Reviewed Original ResearchMeSH KeywordsAmitriptylineAnalysis of VarianceAnimalsAntidepressive Agents, TricyclicBehavior, AnimalBromodeoxyuridineCell CountCell ProliferationDose-Response Relationship, DrugDrosophila ProteinsDrug InteractionsHelplessness, LearnedHindlimb SuspensionHippocampusImmunohistochemistryMecamylamineMiceMice, Inbred C57BLMice, KnockoutNeuronsNicotinic AntagonistsNortriptylineReceptors, NicotinicSwimmingConceptsHigh-affinity nAChRsHippocampal cell proliferationNicotinic acetylcholine receptorsSwim testAcetylcholine receptorsCell proliferationHigh-affinity nicotinic acetylcholine receptorsNoncompetitive nAChR antagonist mecamylamineAntagonism of nAChRsAntidepressant-induced increasesAntidepressant-like effectsNAChR antagonist mecamylamineWild-type miceInhibition of nAChRsAntidepressants actAntidepressant actionAntidepressant effectsChronic treatmentAntagonist mecamylamineAntidepressant propertiesTricyclic antidepressantsAntidepressant activityTherapeutic effectKnockout miceNoncompetitive antagonistβ2-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
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
2001
Nicotinic 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
1999
Two pharmacologically distinct components of nicotinic receptor-mediated rubidium efflux in mouse brain require the beta2 subunit.
Marks MJ, Whiteaker P, Calcaterra J, Stitzel JA, Bullock AE, Grady SR, Picciotto MR, Changeux JP, Collins AC. Two pharmacologically distinct components of nicotinic receptor-mediated rubidium efflux in mouse brain require the beta2 subunit. Journal Of Pharmacology And Experimental Therapeutics 1999, 289: 1090-103. PMID: 10215692.Peer-Reviewed Original ResearchConceptsBeta2 subunitBeta2 null mutant miceConcentration-effect curvesMouse brain synaptosomesAlpha4beta2 receptorsBrain synaptosomesNicotinic agonistsMouse brainRubidium effluxMutant miceLine radioactivity detectionDHbetaEAgonistsEffluxBrainStimulationRadioactivity detectionPotencyHexamethoniumErythroidineResponseAcetylcholineMethyllycaconitineAntagonistBungarotoxin