2020
Implications of Oligomeric Amyloid-Beta (oAβ42) Signaling through α7β2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline
George AA, Vieira JM, Xavier-Jackson C, Gee MT, Cirrito JR, Bimonte-Nelson HA, Picciotto MR, Lukas RJ, Whiteaker P. Implications of Oligomeric Amyloid-Beta (oAβ42) Signaling through α7β2-Nicotinic Acetylcholine Receptors (nAChRs) on Basal Forebrain Cholinergic Neuronal Intrinsic Excitability and Cognitive Decline. Journal Of Neuroscience 2020, 41: 555-575. PMID: 33239400, PMCID: PMC7821864, DOI: 10.1523/jneurosci.0876-20.2020.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBasal ForebrainCell LineCognitive DysfunctionElectrophysiological PhenomenaFemaleGenotypeHumansMaleMaze LearningMiceMice, TransgenicNeuronsParasympathetic Nervous SystemPeptide FragmentsSignal TransductionConceptsBasal forebrain cholinergic neuronsNeuronal intrinsic excitabilityAlzheimer's diseaseCholinergic neuronsDiagonal bandIntrinsic excitabilityAPP/PS1 transgenic miceCognitive declineCharacteristics of ADMedial septum-diagonal bandNicotinic acetylcholine receptor subtypesOligomeric amyloid betaAction potential firing rateForebrain cholinergic neuronsPS1 transgenic miceHorizontal diagonal bandLevels of amyloidSeptum-diagonal bandCurrent-clamp recordingsAcetylcholine receptor subtypesAction potential afterhyperpolarizationAge-matched littermatesOrganotypic slice culturesSpatial reference memoryHomomeric α7
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 ResearchMeSH KeywordsAggressionAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBenzylidene CompoundsGenes, Immediate-EarlyHippocampusMaleMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicNeuronsNicotinic AgonistsPyridinesConceptsΑ7 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 activityHippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice
Mineur YS, Mose TN, Blakeman S, Picciotto MR. Hippocampal α7 nicotinic ACh receptors contribute to modulation of depression‐like behaviour in C57BL/6J mice. British Journal Of Pharmacology 2017, 175: 1903-1914. PMID: 28264149, PMCID: PMC5979617, DOI: 10.1111/bph.13769.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBehavior, AnimalDepressionFemaleHippocampusMaleMiceMice, Inbred C57BLPhysostigmineConceptsDepression-like behaviorNicotinic ACh receptorsFemale miceMale miceCholinergic signalingACh receptorsΑ7 nAChRsSignificant antidepressant-like effectΑ7 nicotinic ACh receptorsEffect of α7Antidepressant-like effectsAgonist GTS-21Depression-related behaviorsC-Fos immunoreactivityACh receptor antagonistDepression-like phenotypeAnxiety-like behaviorNicotinic acetylcholine receptorsAnxiety-like phenotypeHippocampal α7Physostigmine administrationAntagonist methyllycaconitineReceptor antagonistSwim testGTS-21
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 ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAmygdalaAnimalsMaleMecamylamineMiceMice, Inbred C57BLMice, KnockoutNicotinic AntagonistsPhysostigmineReceptors, NicotinicSignal TransductionStress, PsychologicalConceptsDepression-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 infusion
2013
Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 12078-12083. PMID: 23818597, PMCID: PMC3718126, DOI: 10.1073/pnas.1307849110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnalysis of VarianceAnimalsBridged Bicyclo Compounds, HeterocyclicCholinergic AgonistsCholinergic AntagonistsCognitionFemaleIontophoresisMacaca mulattaMaleMecamylamineMicroscopy, ImmunoelectronN-MethylaspartatePhenolsPiperidinesPrefrontal CortexQuinuclidinesReceptors, NicotinicSpatial BehaviorSynapsesVisual PerceptionConceptsDorsolateral prefrontal cortexΑ7 nAChRsPrefrontal cortexΑ7 nicotinic acetylcholine receptorGlutamatergic NMDA receptorsCognitive circuitsNicotinic α7 receptorsPrimary visual cortexNMDA receptor actionGenetic insultsNicotinic acetylcholine receptorsDlPFC circuitsPrimate dlPFCACh depletionNMDA actionNMDA receptorsPyramidal cellsΑ7 receptorsNeuronal firingNAChR blockadeAcetylcholine receptorsVisual cortexPersistent firingCognitive functionLow-dose stimulation
2010
Modulation 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 ResearchMeSH KeywordsAlcohol DrinkingAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBenzazepinesChoice BehaviorDose-Response Relationship, DrugDrinking BehaviorFemaleMaleMiceMice, Inbred C57BLMice, KnockoutNicotinic AgonistsQuinoxalinesReceptors, NicotinicVareniclineConceptsEffects 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
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 ResearchMeSH KeywordsAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBrain MappingCocaineDihydro-beta-ErythroidineDopamineDrug InteractionsMaleMiceMice, Inbred C57BLMicrodialysisNicotinic AntagonistsNucleus AccumbensReceptors, NicotinicVentral Tegmental AreaConceptsIntra-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 ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsAntidepressive AgentsFemaleHindlimb SuspensionMaleMecamylamineMiceMice, Inbred C57BLMice, KnockoutMotor ActivityNicotinic AntagonistsReceptors, NicotinicConceptsAntidepressant-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 ResearchMeSH KeywordsAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBasal GangliaCentral Nervous System StimulantsCocaineDopamineExtracellular FluidMaleMecamylamineMiceMice, Inbred C57BLMice, KnockoutNicotinic AntagonistsReceptors, NicotinicConceptsExtracellular 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
2003
Neuroprotection by Nicotine in Mouse Primary Cortical Cultures Involves Activation of Calcineurin and L-Type Calcium Channel Inactivation
Stevens TR, Krueger SR, Fitzsimonds RM, Picciotto MR. Neuroprotection by Nicotine in Mouse Primary Cortical Cultures Involves Activation of Calcineurin and L-Type Calcium Channel Inactivation. Journal Of Neuroscience 2003, 23: 10093-10099. PMID: 14602824, PMCID: PMC6740855, DOI: 10.1523/jneurosci.23-31-10093.2003.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAnimalsBungarotoxinsCalcineurinCalcineurin InhibitorsCalcium Channel BlockersCalcium Channels, L-TypeCells, CulturedCerebral CortexGlutamic AcidMiceMice, KnockoutNeuronsNeuroprotective AgentsNeurotoxinsNicotineNifedipineReceptors, NicotinicTacrolimusConceptsPrimary cortical culturesL-type channelsNicotine-mediated neuroprotectionCortical culturesNicotine pretreatmentIntracellular calciumCalcium influxActivation of calcineurinBeta2 subunitAlpha7-containing nAChRsL-type calcium channelsEffects of nicotineAbility of nicotineMouse primary cortical culturesNicotinic acetylcholine receptorsCalcium channel inactivationGlutamate excitotoxicityNeuroprotective effectsRole of calciumCalcineurin antagonistsCortical neuronsNeuronal excitabilityGlutamate applicationNeuroprotectionCalcium channels