2022
ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms
Mineur YS, Mose TN, Maibom KL, Pittenger ST, Soares AR, Wu H, Taylor SR, Huang Y, Picciotto MR. ACh signaling modulates activity of the GABAergic signaling network in the basolateral amygdala and behavior in stress-relevant paradigms. Molecular Psychiatry 2022, 27: 4918-4927. PMID: 36050437, PMCID: PMC10718266, DOI: 10.1038/s41380-022-01749-7.Peer-Reviewed Original ResearchConceptsBasolateral amygdalaBLA neuronsBalance of inhibitoryHuman mood disordersLight-dark boxGABA interneuronsPV neuronsVIP neuronsCalmodulin-dependent protein kinase IIMale miceACh levelsMood disordersTail suspensionNeuronal activityNeuron subtypesAcetylcholineChronic stressInhibitory signalingBalance of activityHomeostatic functionsBLA activityStress-induced changesNeuronsSocial defeatProtein kinase II
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 α7Effects of nicotine on DARPP-32 and CaMKII signaling relevant to addiction
Lee AM, Picciotto MR. Effects of nicotine on DARPP-32 and CaMKII signaling relevant to addiction. Advances In Pharmacology 2020, 90: 89-115. PMID: 33706940, PMCID: PMC8008986, DOI: 10.1016/bs.apha.2020.09.002.Peer-Reviewed Original ResearchConceptsKey intracellular signaling cascadesIntracellular signaling cascadesDependent kinase IIPaul GreengardSignaling cascadesKinase IINicotine-dependent behaviorsNicotinic acetylcholine receptorsSecond messenger systemsNeuronal signalingInitial characterizationDARPP-32ProteinMessenger systemsAcetylcholine receptorsSignalingRoleCaMKIIGreengardNicotine addictionCascadeImmunohistochemical workDiscoveryReceptorsCAMP
2019
Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake
Calarco CA, Picciotto MR. Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine’s Effects on Food Intake. Nicotine & Tobacco Research 2019, 22: 152-163. PMID: 30690485, PMCID: PMC7297099, DOI: 10.1093/ntr/ntz010.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsFood intakeNicotinic acetylcholine receptorsWeight gainBody weightPreclinical workAcetylcholine receptorsPost-cessation weight gainOrexigenic agouti-related peptideAnorexigenic proopiomelanocortin (POMC) neuronsNicotine replacement therapyAgouti-related peptideNicotinic agonist cytisineAbility of nicotineLower body weightProopiomelanocortin neuronsNicotine administrationHypothalamic circuitsReplacement therapyArcuate nucleusNicotine effectsNicotine actsAgonist cytisineAverage weight gainTobacco useRodent modelsRole of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine
Deyama S, Bang E, Wohleb ES, Li XY, Kato T, Gerhard DM, Dutheil S, Dwyer JM, Taylor SR, Picciotto MR, Duman RS. Role of Neuronal VEGF Signaling in the Prefrontal Cortex in the Rapid Antidepressant Effects of Ketamine. American Journal Of Psychiatry 2019, 176: 388-400. PMID: 30606046, PMCID: PMC6494682, DOI: 10.1176/appi.ajp.2018.17121368.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, NeutralizingBehavior, AnimalExcitatory Amino Acid AntagonistsGene Knockdown TechniquesGene Knockout TechniquesIn Vitro TechniquesKetamineMiceNeuronsPrefrontal CortexQuinazolinesSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsNeuronal vascular endothelial growth factorVascular endothelial growth factorMedial prefrontal cortexRapid antidepressant actionsAntidepressant actionIntra-mPFC infusionSystemic ketamineBehavioral actionsFlk-1Conventional monoamine-based antidepressantsPrefrontal cortexRole of VEGFRapid antidepressant effectsTreatment-resistant depressionMethyl-d-aspartate receptor antagonist ketamineNeuron-specific deletionMonoamine-based antidepressantsNeuron-specific knockoutViral-mediated knockdownEndothelial growth factorVEGF-Flk-1Synaptogenic actionsAntidepressant effectsSynaptogenic effectsLocal knockdown
2018
Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice
Mineur YS, Cahuzac EL, Mose TN, Bentham MP, Plantenga ME, Thompson DC, Picciotto MR. Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology 2018, 43: 2118-2125. PMID: 29472646, PMCID: PMC6098039, DOI: 10.1038/s41386-018-0024-x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAdrenergic alpha-AgonistsAlkaloidsAmygdalaAnimalsAnxietyAzocinesCholinesterase InhibitorsDepressionFemaleGene Knockdown TechniquesGuanfacineMaleMiceMice, Inbred C57BLNicotinic AgonistsNorepinephrineParasympathetic Nervous SystemQuinolizinesReceptors, Adrenergic, alpha-2Signal TransductionSympathetic Nervous SystemConceptsAntidepressant-like effectsNoradrenergic systemMale C57BL/6J miceDepression-related behaviorsDepression-like phenotypeNicotinic acetylcholine receptorsAntidepressant efficacyCholinergic interactionsNE terminalsC57BL/6J miceShRNA-mediated knockdownAgonist guanfacineAgonist cytisineClinical studiesSmoking relapseΑ2A receptorsAcute abstinenceBrain areasAcetylcholine receptorsAcetylcholineGuanfacineAmygdalaBehavioral effectsAnxiety disordersStress pathways
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 infusion
2013
Morphine dependence and withdrawal induced changes in cholinergic signaling
Neugebauer NM, Einstein EB, Lopez MB, McClure-Begley TD, Mineur YS, Picciotto MR. Morphine dependence and withdrawal induced changes in cholinergic signaling. Pharmacology Biochemistry And Behavior 2013, 109: 77-83. PMID: 23651795, PMCID: PMC3690589, DOI: 10.1016/j.pbb.2013.04.015.Peer-Reviewed Original ResearchConceptsMedial habenulaMorphine dependenceCholinergic signalingInterpeduncular nucleusHigh-affinity nicotinic acetylcholine receptorsNicotinic acetylcholine receptor levelsEffects of cholinergicMorphine-dependent miceChronic morphine administrationAcetylcholine receptor levelsC-fos expressionC-Fos activationNicotinic acetylcholine receptorsDependent miceMorphine administrationMorphine withdrawalCholinergic drugsOpiate withdrawalCholinergic systemEpibatidine bindingReceptor levelsSomatic signsNeuronal activityAcetylcholine receptorsNAChR receptorCholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior
Mineur YS, Obayemi A, Wigestrand MB, Fote GM, Calarco CA, Li AM, Picciotto MR. Cholinergic signaling in the hippocampus regulates social stress resilience and anxiety- and depression-like behavior. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 3573-3578. PMID: 23401542, PMCID: PMC3587265, DOI: 10.1073/pnas.1219731110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholinesteraseAnimalsAntidepressive AgentsAnxietyBehavior, AnimalCholinergic AntagonistsCholinergic NeuronsDependovirusDepressionFluoxetineGene Knockdown TechniquesHindlimb SuspensionHippocampusHumansMaleMiceMice, Inbred C57BLPhenotypePhysostigmineReceptors, CholinergicResilience, PsychologicalRNA, Small InterferingSignal TransductionStress, PsychologicalTime FactorsConceptsDepression-like behaviorShRNA-mediated knockdownSelective serotonin reuptake inhibitor fluoxetineSerotonin reuptake inhibitor fluoxetineAChE inhibitor physostigmineAdministration of fluoxetineBlockade of acetylcholinesteraseEndophenotypes of depressionHippocampal AChE activityAntidepressant-like effectsReuptake inhibitor fluoxetineAChE activityDepression-like phenotypeSymptoms of depressionSocial defeat paradigmHippocampal AChEMuscarinic antagonistCholinergic drugsInhibitor physostigmineCholinergic systemClinical trialsSystemic administrationMood disordersSystemic effectsAnimal models
2012
Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior. Neuron 2012, 76: 116-129. PMID: 23040810, PMCID: PMC3466476, DOI: 10.1016/j.neuron.2012.08.036.Peer-Reviewed Original ResearchConceptsBrain areasAlters neuronal excitabilityAbility of acetylcholineNeuronal networksNervous system functionGroups of neuronsCholinergic modulationReceptor subtypesNeuronal excitabilityFood intakeSynaptic transmissionNeuronal populationsSynaptic plasticityAcetylcholineSynaptic propertiesDrug abuseSite of releaseNeuromodulatorsClassical roleOngoing stimulusNeuronsDiverse effectsSystem functionResponseCholinergic
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 excitation
2010
Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference
Neugebauer NM, Henehan RM, Hales CA, Picciotto MR. Mice lacking the galanin gene show decreased sensitivity to nicotine conditioned place preference. Pharmacology Biochemistry And Behavior 2010, 98: 87-93. PMID: 21172385, PMCID: PMC3030658, DOI: 10.1016/j.pbb.2010.12.015.Peer-Reviewed Original ResearchConceptsGal-/- miceAcute nicotine administrationNicotine CPPPlace preferenceNicotine administrationRewarding effectsRole of galaninEffects of nicotineNucleus accumbens shellClass of drugsAmphetamine place preferenceDrugs of abuseGalanin signalingNeuropeptide galaninCPP chamberAlcohol drinkingNicotine rewardSignificant CPPExtracellular signal-related kinaseAccumbens shellGalanin peptideHigh doseSystem activationAlcohol preferenceSignal-related kinaseNicotine 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
2008
Molecular Mechanisms Underlying the Motivational Effects of Nicotine
Brunzell DH, Picciotto MR. Molecular Mechanisms Underlying the Motivational Effects of Nicotine. Nebraska Symposium On Motivation 2008, 55: 17-30. PMID: 19013937, PMCID: PMC3594851, DOI: 10.1007/978-0-387-78748-0_3.Peer-Reviewed Original ResearchAdministration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats
Addy NA, Bahi A, Taylor JR, Picciotto MR. Administration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats. Psychopharmacology 2008, 200: 129-139. PMID: 18587562, PMCID: PMC2574760, DOI: 10.1007/s00213-008-1189-5.Peer-Reviewed Original ResearchConceptsLocomotor responseCocaine 5Cocaine injectionLocomotor activityCocaine-induced locomotor activityAcute locomotor responseAcute cocaine challengeMale Sprague-DawleyCocaine-mediated behaviorsCyclosporine administrationMethodsLocomotor activityCalcineurin inhibitorsDaily administrationI. AdministrationCocaine challengeCocaine exposureSprague-DawleyCyclosporine pretreatmentAbility of calcineurinConclusionOur resultsCocaine-mediated changesAdministrationCocaineSynapsin IPotential mechanismsGalanin – 25 years with a multitalented neuropeptide
Picciotto MR. Galanin – 25 years with a multitalented neuropeptide. Cellular And Molecular Life Sciences 2008, 65: 1872-1879. PMID: 18500649, PMCID: PMC11131873, DOI: 10.1007/s00018-008-8151-x.Peer-Reviewed Original ResearchConceptsGalanin receptorsFood intakeOpiate rewardDrug rewardGalanin – 25 yearsAbility of neuropeptidesMesolimbic dopamine systemDrugs of abuseGalanin agonistsNoradrenergic neuronsDrug withdrawalStriatal slicesWithdrawal signsAnalgesic propertiesLocus coeruleusHypothalamic functionDopamine releaseDopamine systemGalaninNovel treatmentsPlace preferenceStress-related pathwaysFiring ratePotential targetWithdrawalNeuroprotection 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 ResearchMeSH KeywordsAffectAnimalsDown-RegulationHumansNicotineNicotinic AgonistsReceptors, NicotinicRewardSignal TransductionTobacco Use DisorderUp-RegulationConceptsDesensitization 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 effectsNAChRsDesensitizationDeficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice
Smith K, Fagel DM, Stevens HE, Rabenstein RL, Maragnoli ME, Ohkubo Y, Picciotto MR, Schwartz ML, Vaccarino FM. Deficiency in Inhibitory Cortical Interneurons Associates with Hyperactivity in Fibroblast Growth Factor Receptor 1 Mutant Mice. Biological Psychiatry 2007, 63: 953-962. PMID: 17988653, DOI: 10.1016/j.biopsych.2007.09.020.Peer-Reviewed Original ResearchMeSH KeywordsAmphetamineAnimalsBehavior, AnimalBiogenic MonoaminesCell CountCentral Nervous System StimulantsCerebral CortexDisease Models, AnimalDopamine AgentsExploratory BehaviorFibroblast Growth Factor 1Glutamate DecarboxylaseHyperkinesisLocomotionMaleMethylphenidateMiceMice, KnockoutMotor ActivityNerve Tissue ProteinsNeural InhibitionNeuronsSignal TransductionConceptsInhibitory cortical circuitsCortical pyramidal neuronsD2 receptor antagonistGrowth factor receptor 1Spontaneous locomotor hyperactivityFibroblast growth factor receptor 1Factor receptor 1Inhibitory neuronal subtypesLocomotor hyperactivityDopamine agonistsCerebral cortexPyramidal neuronsBasal gangliaMotor hyperactivityReceptor antagonistInhibitory interneuronsTyrosine hydroxylaseCortical circuitsPsychiatric disordersLocomotor responseNeuronal subtypesReceptor 1Mutant miceDopamine transporterSpatial learningGalanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward
Hawes JJ, Brunzell DH, Narasimhaiah R, Langel Ű, Wynick D, Picciotto MR. Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward. Neuropsychopharmacology 2007, 33: 1864-1873. PMID: 17957220, PMCID: PMC2504505, DOI: 10.1038/sj.npp.1301579.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBlotting, WesternBrain ChemistryConditioning, OperantCyclic AMP Response Element-Binding ProteinDose-Response Relationship, DrugExtracellular Signal-Regulated MAP KinasesGalaninGenotypeMiceMice, KnockoutMorphineMorphine DependenceMotor ActivityNarcoticsRewardSignal TransductionConceptsGKO miceMorphine place preferenceOpiate rewardGalanin agonistsMorphine administrationPlace preferenceGalanin knockout miceSingle systemic injectionEndogenous negative regulatorDrugs of abuseAcute administrationNeurochemical effectsNeuropeptide galaninPeripheral injectionWithdrawal signsLocomotor activationSystemic injectionNeurochemical correlatesNucleus accumbensGalaninKnockout miceTherapeutic targetBrain areasDrug reinforcementGalnon