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
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsFeeding BehaviorHypothalamusMaleMiceMice, TransgenicNerve NetNeuronsObesityOrexinsStress, PsychologicalConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeuronsCumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity
Barthas F, Hu MY, Siniscalchi MJ, Ali F, Mineur YS, Picciotto MR, Kwan AC. Cumulative Effects of Social Stress on Reward-Guided Actions and Prefrontal Cortical Activity. Biological Psychiatry 2020, 88: 541-553. PMID: 32276717, PMCID: PMC7434704, DOI: 10.1016/j.biopsych.2020.02.008.Peer-Reviewed Original ResearchConceptsPrefrontal cortical activityCortical activityIndividual layer 2/3 pyramidal neuronsLayer 2/3 pyramidal neuronsStress exposureDepressive-like phenotypeTwo-photon calcium imagingSocial stressChronic social stressIndividual prefrontal neuronsMedial prefrontal cortexPyramidal neuronsMotor subregionsNeural dysfunctionResilient miceCalcium imagingPrefrontal neuronsAbnormal levelsPrefrontal cortexSocial defeatDistinct neural responsesStress-induced lossGoal-directed actionsEnsemble activityDefeat sessions
2019
Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine
Lee AM, Calarco CA, McKee SA, Mineur YS, Picciotto MR. Variability in nicotine conditioned place preference and stress‐induced reinstatement in mice: Effects of sex, initial chamber preference, and guanfacine. Genes Brain & Behavior 2019, 19: e12601. PMID: 31364813, PMCID: PMC8045136, DOI: 10.1111/gbb.12601.Peer-Reviewed Original ResearchConceptsStress-induced reinstatementEffects of guanfacinePlace preferenceFemale miceInfralimbic cortexArc immunoreactivityΑ2-adrenergic receptor agonistAnterior insulaNeurobiological mechanismsLateral central amygdalaNovel treatment optionsChamber preferencePlace preference acquisitionSex-dependent changesStress-induced relapseDose-response patternNucleus accumbens coreNicotine-dependent behaviorsSmoking occursTreatment optionsNicotine rewardReceptor agonistCentral amygdalaNeuronal activationPreclinical studies
2017
Effect of doxazosin on stress reactivity and the ability to resist smoking
Verplaetse TL, Weinberger AH, Oberleitner LM, Smith KM, Pittman BP, Shi JM, Tetrault JM, Lavery ME, Picciotto MR, McKee SA. Effect of doxazosin on stress reactivity and the ability to resist smoking. Journal Of Psychopharmacology 2017, 31: 830-840. PMID: 28440105, PMCID: PMC5823502, DOI: 10.1177/0269881117699603.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AntagonistsAdultCravingDoxazosinFemaleHumansMaleMiddle AgedPilot ProjectsSmokingStress, PsychologicalConceptsTobacco cravingCortisol levelsSubsequent ad libitum smokingEffects of doxazosinAd libitum smokingNumber of cigarettesNicotine-motivated behaviorsSmoking lapse behaviorΑ1-adrenergic antagonistNicotine-deprived smokersTitration periodPreclinical findingsSmoking cessationNoradrenergic systemTreatment strategiesDoxazosinSmoking behaviorSmokingHuman laboratoryPhysiologic reactivityPilot studyStress reactivityEffects of stressCigarettesStress imagery
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
2014
A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation
McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten A, Picciotto MR, Weinberger AH, Ashare R, Sinha R. A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation. Journal Of Psychopharmacology 2014, 29: 300-311. PMID: 25516371, PMCID: PMC4376109, DOI: 10.1177/0269881114562091.Peer-Reviewed Original ResearchConceptsPlacebo-treated subjectsFunctional magnetic resonance imagingCentral noradrenergic pathwaysPrefrontal cognitive dysfunctionSystolic blood pressureClinical outcome dataAd libitum smokingNovel translational approachStress-induced reinstatementMagnetic resonance imagingNicotine-deprived smokersBlood pressureNoradrenergic pathwaysAgonist guanfacineCognitive dysfunctionTreatment periodTobacco cravingQuit attemptsOutcome dataSmokingComplete abstinenceCortisol levelsTranslational investigationsCigarette useGuanfacineExpression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine
Mineur YS, Einstein EB, Bentham MP, Wigestrand MB, Blakeman S, Newbold SA, Picciotto MR. Expression of the 5-HT1A Serotonin Receptor in the Hippocampus Is Required for Social Stress Resilience and the Antidepressant-Like Effects Induced by the Nicotinic Partial Agonist Cytisine. Neuropsychopharmacology 2014, 40: 938-946. PMID: 25288485, PMCID: PMC4330507, DOI: 10.1038/npp.2014.269.Peer-Reviewed Original ResearchMeSH Keywords8-Hydroxy-2-(di-n-propylamino)tetralinAlkaloidsAnimalsAntidepressive AgentsAzocinesDisease Models, AnimalDrug SynergismFluoxetineGene Expression RegulationHEK293 CellsHindlimb SuspensionHippocampusHumansInterpersonal RelationsMaleMiceMice, Inbred C57BLMotor ActivityQuinolizinesReceptor, Serotonin, 5-HT1ASelective Serotonin Reuptake InhibitorsSerotonin Receptor AgonistsStress, PsychologicalConceptsAntidepressant-like effectsSelective serotonin reuptake inhibitorsDorsal rapheCholinergic systemAgonist cytisineNicotinic acetylcholine receptor blockersEffects of cytisineTreatment-resistant patientsSerotonin reuptake inhibitorsAcetylcholine receptor blockerSSRI fluoxetineReceptor blockersAntidepressant efficacyReuptake inhibitorsSerotonin depletionCholinergic drugsMood disordersSerotonin receptorsMouse modelPharmacological approachesHippocampusReceptorsCytisineRapheMolecular mechanisms
2013
Mediating Role of Stress Reactivity in the Effects of Prenatal Tobacco Exposure on Childhood Mental Health Outcomes
Park A, O’Malley S, King SL, Picciotto MR. Mediating Role of Stress Reactivity in the Effects of Prenatal Tobacco Exposure on Childhood Mental Health Outcomes. Nicotine & Tobacco Research 2013, 16: 174-185. PMID: 23990474, PMCID: PMC3880234, DOI: 10.1093/ntr/ntt131.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultChildChild Behavior DisordersChild, PreschoolChi-Square DistributionConfounding Factors, EpidemiologicFemaleHumansLongitudinal StudiesMaleMental DisordersMothersPregnancyPrenatal Exposure Delayed EffectsProspective StudiesRisk FactorsSmokingStress, PsychologicalSurveys and QuestionnairesUnited KingdomYoung AdultConceptsMental health outcomesStressful life eventsPrenatal tobacco exposureAdverse mental health outcomesStress reactivityLife eventsMothers' ratingsChildhood mental health outcomesTobacco exposureChildren's reactivityHealth outcomesMiddle childhoodEmotional problemsAvon Longitudinal StudyDifficulties QuestionnairePreschool ageAge 4Mental healthLongitudinal studyProspective population-based studyLarge prospective population-based studyPsychiatric symptomsEarly childhoodPopulation-based studyRatingsCholinergic 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
2009
Effects of galanin on monoaminergic systems and HPA axis: Potential mechanisms underlying the effects of galanin on addiction- and stress-related behaviors
Picciotto MR, Brabant C, Einstein EB, Kamens HM, Neugebauer NM. Effects of galanin on monoaminergic systems and HPA axis: Potential mechanisms underlying the effects of galanin on addiction- and stress-related behaviors. Brain Research 2009, 1314: 206-218. PMID: 19699187, PMCID: PMC2819596, DOI: 10.1016/j.brainres.2009.08.033.Peer-Reviewed Original ResearchConceptsEffects of galaninStress-related behaviorsDrugs of abuseGalanin receptorsAbility of galaninPotential mechanismsAddiction-related disordersDrug-related behaviorsNumber of neuropeptidesGalanin effectsHPA axisMonoaminergic systemsDrug exposureTreatment of stressNeuronal activityGalaninBrain areasNeuronal functionBrain regionsAddictive drugsBrain circuitsNovel therapeuticsDrugsNeural activityReceptors
2007
Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors
Elsworth JD, Morrow BA, Nguyen V, Mitra J, Picciotto MR, Roth RH. Prenatal cocaine exposure enhances responsivity of locus coeruleus norepinephrine neurons: Role of autoreceptors. Neuroscience 2007, 147: 419-427. PMID: 17543464, PMCID: PMC2855228, DOI: 10.1016/j.neuroscience.2007.04.036.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoradiographyAutoreceptorsClonidineCocaineFemaleGenes, fosImmunohistochemistryInjections, IntravenousLocus CoeruleusMaleNeuronsNorepinephrinePrefrontal CortexPregnancyPrenatal Exposure Delayed EffectsRadioligand AssayRatsRats, Sprague-DawleyStress, PsychologicalTyrosine 3-MonooxygenaseConceptsPrenatal cocaine exposureNorepinephrine neuronsCocaine exposurePrenatal cocaineTyrosine hydroxylase-positive neuronsLocus coeruleus norepinephrine neuronsPrenatal cocaine exposure resultsPrenatal saline controlsRole of autoreceptorsLocus coeruleus noradrenergic systemPrenatal treatment groupsCocaine exposure resultsAlpha2-adrenergic receptorsInjection of cocaineGestational day 10Pharmacology of cocaineDaily i.LC neuronsNorepinephrine turnoverPregnant ratsNeurobehavioral deficitsSaline controlsFos expressionNoradrenergic systemRat model
2006
Antidepressant-Like Effects of Ceftriaxone in Male C57BL/6J Mice
Mineur YS, Picciotto MR, Sanacora G. Antidepressant-Like Effects of Ceftriaxone in Male C57BL/6J Mice. Biological Psychiatry 2006, 61: 250-252. PMID: 16860779, DOI: 10.1016/j.biopsych.2006.04.037.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMajor depressive disorderUptake of glutamateBeta-lactam antibiotic agentsNovelty-suppressed feeding testExcessive glutamatergic neurotransmissionDepressive-like behaviorAntidepressant-like activityMale C57BL/6J miceTail suspension testNovelty-suppressed feedingCeftriaxone treatmentC57BL/6J miceGlutamatergic neurotransmissionDepressive disorderAntidepressant compoundsSuspension testMouse modelThree monthsCeftriaxoneAntibiotic agentsRecent evidenceMiceSimilar effectsFeeding testsGalanin: a novel therapeutic target for depression, anxiety disorders and drug addiction?
Holmes A, Picciotto MR. Galanin: a novel therapeutic target for depression, anxiety disorders and drug addiction? CNS & Neurological Disorders - Drug Targets 2006, 5: 225-32. PMID: 16611095, DOI: 10.2174/187152706776359600.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxiety DisordersBiogenic AminesBrainDepressive DisorderGalaninHumansStress, PsychologicalSubstance Withdrawal SyndromeSubstance-Related DisordersConceptsStress-related neural pathwaysBrain stress pathwaysSerotonin-producing neuronsDistribution of galaninDepression-related behaviorsDorsal raphe nucleusExpression of galaninAdministration of galaninNovel therapeutic targetDrug addictionPotential roleAnxiety-like responsesGalanin agonistsGalanin systemRaphe nucleusDopamine neuronsOpiate withdrawalLocus coeruleusNeuronal typesRodent modelsCurrent evidenceGalaninPsychiatric disordersTherapeutic targetOpiate reinforcement
2001
Effects of nicotine pretreatment on dopaminergic and behavioral responses to conditioned fear stress in rats: dissociation of biochemical and behavioral effects
George T, Picciotto M, Verrico C, Roth R. Effects of nicotine pretreatment on dopaminergic and behavioral responses to conditioned fear stress in rats: dissociation of biochemical and behavioral effects. Biological Psychiatry 2001, 49: 300-306. PMID: 11230881, DOI: 10.1016/s0006-3223(00)00928-8.Peer-Reviewed Original ResearchConceptsConditioned fear stressNicotine pretreatmentMedial prefrontal cortexFear stressDopamine metabolismNucleus accumbensPrefrontal cortexAcute footshock stressImmobility responseBehavioral responsesCortical dopaminergicDopamine utilizationCortical dopamineNicotine exposureFootshock stressNicotine dependenceAnxiolytic activityConditioned fear paradigmNicotine differsDay 21Psychological stressorsBehavioral effectsDopaminergicClinical contextPreferential activation