2020
Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses
Fogaça MV, Wu M, Li C, Li XY, Picciotto MR, Duman RS. Inhibition of GABA interneurons in the mPFC is sufficient and necessary for rapid antidepressant responses. Molecular Psychiatry 2020, 26: 3277-3291. PMID: 33070149, PMCID: PMC8052382, DOI: 10.1038/s41380-020-00916-y.Peer-Reviewed Original ResearchConceptsGABA interneuronsRapid antidepressant responseMajor depressive disorderAntidepressant effectsSynaptic plasticityAntidepressant responseRapid-acting antidepressantsAcetylcholine muscarinic receptor antagonistMuscarinic receptor antagonistCortical brain areasEffects of scopolamineAntidepressant actionChemogenetic inhibitionGABAergic interneuronsReceptor antagonistDepressive disorderMale miceInterneuron subtypesBrain areasInterneuronsMPFCTransient inhibitionAffective behaviorInhibitionSubtypes
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
Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice
Mineur YS, Bentham MP, Zhou WL, Plantenga ME, McKee SA, Picciotto MR. Antidepressant-like effects of guanfacine and sex-specific differences in effects on c-fos immunoreactivity and paired-pulse ratio in male and female mice. Psychopharmacology 2015, 232: 3539-3549. PMID: 26146014, PMCID: PMC4561580, DOI: 10.1007/s00213-015-4001-3.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsPaired-pulse ratioC-Fos immunoreactivityPrefrontal cortexSwim testBrain areasRobust antidepressant-like effectsBrain regionsSex differencesMale C57BL/6J miceDepression-like behaviorEffects of guanfacineAcetylcholinesterase inhibitor physostigmineLight/dark boxBaseline sex differencesC-fos expressionDepression-like stateCritical brain regionsDifferent brain areasSex-specific changesAntidepressant efficacyCholinergic controlInhibitor physostigmineC57BL/6J miceAgonist guanfacine
2014
Calcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice
Mineur YS, Taylor SR, Picciotto MR. Calcineurin Downregulation in the Amygdala Is Sufficient to Induce Anxiety-like and Depression-like Behaviors in C57BL/6J Male Mice. Biological Psychiatry 2014, 75: 991-998. PMID: 24742621, PMCID: PMC4037359, DOI: 10.1016/j.biopsych.2014.03.009.Peer-Reviewed Original ResearchConceptsDepression-like behaviorOrgan transplant patientsAnxiety-like behaviorTransplant patientsMood disordersCalcineurin activityIncidence of anxietyCalcineurin inhibitor cyclosporine ALight/dark boxPotential clinical consequencesOpen field testSymptoms of anxietyChronic blockadeChronic administrationTransplant rejectionCsA treatmentRole of calcineurinSystemic inhibitionMale miceClinical consequencesCyclosporine ACalcineurin levelsBrain areasCalcium-dependent phosphatase calcineurinGene transfer approach
2012
Constitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine
Jung Y, Mulholland PJ, Wiseman SL, Chandler LJ, Picciotto MR. Constitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine. European Journal Of Neuroscience 2012, 37: 1-9. PMID: 23106536, PMCID: PMC3538958, DOI: 10.1111/ejn.12037.Peer-Reviewed Original ResearchConceptsNucleus accumbensCocaine administrationSpine densitySynaptic plasticityMature mushroom-shaped spinesMushroom spine densityDaily cocaine administrationMushroom-shaped spinesChronic cocaine administrationOverall spine densityElevated locomotor activityExperience-dependent remodelingLipophilic dye DiINAc slicesWT miceMushroom spinesKO miceCocaine treatmentDiolistic labelingSynaptic remodelingBrain slicesBrain areasConstitutive knockoutMature spinesLocomotor activityAcetylcholine 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
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
2008
Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus
Rao Y, Lu M, Ge F, Marsh DJ, Qian S, Wang AH, Picciotto MR, Gao XB. Regulation of Synaptic Efficacy in Hypocretin/Orexin-Containing Neurons by Melanin Concentrating Hormone in the Lateral Hypothalamus. Journal Of Neuroscience 2008, 28: 9101-9110. PMID: 18784290, PMCID: PMC2562258, DOI: 10.1523/jneurosci.1766-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnalysis of VarianceAnimalsAnimals, NewbornBehavior, AnimalBenzazepinesBenzhydryl CompoundsCentral Nervous System StimulantsDopamine AgonistsDose-Response Relationship, DrugExcitatory Amino Acid AgentsGlutamic AcidGreen Fluorescent ProteinsHypothalamic Area, LateralHypothalamic HormonesIn Vitro TechniquesIntracellular Signaling Peptides and ProteinsMelaninsMiceMice, Inbred C57BLMice, TransgenicModafinilMotor ActivityNeuronsNeuropeptidesOrexinsPertussis ToxinPituitary HormonesReceptors, SomatostatinSynapsesSynaptic TransmissionTime FactorsConceptsHypocretin/orexin neuronsMCHR1 KO miceOrexin-containing neuronsLateral hypothalamusWild-type miceOrexin neuronsHypocretin/orexinKO miceMCH receptor 1Action potential firingEffects of modafinilMelanin-Concentrating HormoneHypocretin/orexin signalingGroups of neuronsMCH neuronsMiniature EPSCsWT miceHypocretin/Glutamatergic synapsesOrexin signalingSynaptic transmissionPertussis toxinBrain areasReciprocal innervationInhibitory influence
2007
Galanin 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
2005
Galanin can attenuate opiate reinforcement and withdrawal
Picciotto MR, Hawes JJ, Brunzell DH, Zachariou V. Galanin can attenuate opiate reinforcement and withdrawal. Neuropeptides 2005, 39: 313-315. PMID: 15944028, DOI: 10.1016/j.npep.2004.12.001.Peer-Reviewed Original ResearchConceptsOpiate reinforcementGalanin receptor agonistAction of opiatesUseful therapeutic agentEndogenous galaninReceptor agonistGalaninKnockout miceBrain areasTransgenic miceBrain regionsBehavioral signsOpiate addictionTherapeutic agentsBody of dataAltered susceptibilityWithdrawalMiceReceptorsAgonistsOpiates
2004
Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain
Hawes JJ, Picciotto MR. Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain. The Journal Of Comparative Neurology 2004, 479: 410-423. PMID: 15514977, DOI: 10.1002/cne.20329.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCatecholaminesGalaninImmunohistochemistryLocus CoeruleusMiceNeural PathwaysNeuronsNucleus AccumbensOpioid-Related DisordersReceptor, Galanin, Type 1Receptor, Galanin, Type 2Receptor, Galanin, Type 3Receptors, GalaninRewardSubstantia NigraTyrosine 3-MonooxygenaseVentral Tegmental AreaConceptsVentral tegmental areaSubstantia nigraLocus coeruleusNucleus accumbensGalanin receptorsBrain areasMouse brainDistribution of immunoreactivityNoradrenergic transmissionGalanin bindingOpiate withdrawalTegmental areaCatecholaminergic nucleiTyrosine hydroxylaseDopamine neurotransmissionGalR1GalR2GalR3BrainProtein levelsDrug addictionGalaninImmunoreactivityReceptorsCoeruleus
2002
Effect of nicotine and nicotinic receptors on anxiety and depression
Picciotto MR, Brunzell DH, Caldarone BJ. Effect of nicotine and nicotinic receptors on anxiety and depression. Neuroreport 2002, 13: 1097-1106. PMID: 12151749, DOI: 10.1097/00001756-200207020-00006.Peer-Reviewed Original ResearchConceptsNicotine treatmentActivation of nAChRsDorsal raphe nucleusEffects of nicotineMesolimbic dopamine systemNicotinic acetylcholine receptorsNicotine administrationMonoaminergic transmissionChronic useRaphe nucleusAnxiolytic actionLateral septumNicotinic receptorsClassical neurotransmittersNormal brainAnimal studiesDopamine systemBrain areasAcetylcholine receptorsNicotineEnsemble of studiesNAChRsAnxiety modelsAdministration studiesDepression
2000
Upregulation of Galanin Binding Sites and GalR1 mRNA Levels in the Mouse Locus Coeruleus Following Chronic Morphine Treatments and Precipitated Morphine Withdrawal
Zachariou V, Thome J, Parikh K, Picciotto M. Upregulation of Galanin Binding Sites and GalR1 mRNA Levels in the Mouse Locus Coeruleus Following Chronic Morphine Treatments and Precipitated Morphine Withdrawal. Neuropsychopharmacology 2000, 23: 127-137. PMID: 10882839, DOI: 10.1016/s0893-133x(00)00094-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAutoradiographyBehavior, AnimalDrug Administration ScheduleFemaleGalaninIn Situ HybridizationIodine RadioisotopesLocus CoeruleusMiceMice, Inbred C57BLMorphineNaltrexoneNucleus AccumbensReceptors, GalaninReceptors, NeuropeptideRNA, MessengerSubstance Withdrawal SyndromeUp-RegulationVentral Tegmental AreaConceptsGalanin binding sitesLocus coeruleusMorphine treatmentMRNA levelsAcute morphine treatmentChronic morphine treatmentMouse locus coeruleusReceptor 1 geneLC neuronsMorphine administrationMorphine withdrawalNeuropeptide galaninOpiate withdrawalReceptor levelsBrain areasDrug dependenceGalaninCAMP levelsWithdrawalBinding sitesCoeruleusTreatmentLevelsGalR1Neurons
1999
Centrally administered galanin blocks morphine place preference in the mouse
Zachariou V, Parikh K, Picciotto M. Centrally administered galanin blocks morphine place preference in the mouse. Brain Research 1999, 831: 33-42. PMID: 10411981, DOI: 10.1016/s0006-8993(99)01476-6.Peer-Reviewed Original ResearchConceptsNucleus accumbensMorphine reinforcementLocus coeruleusSpinal cordPlace preferenceAcute naltrexone administrationGalanin binding sitesQuantitative receptor autoradiographyVentral tegmental areaMorphine place preferencePlace preference paradigmGalaninergic systemMorphine treatmentPeripheral administrationNaltrexone administrationReceptor autoradiographyGalanin bindingOpioid receptorsTegmental areaNeuroendocrine functionGalaninBrain areasDrug dependenceMorphineAversive properties
1998
Identification of Four Classes of Brain Nicotinic Receptors Using β2 Mutant Mice
Zoli M, Léna C, Picciotto M, Changeux J. Identification of Four Classes of Brain Nicotinic Receptors Using β2 Mutant Mice. Journal Of Neuroscience 1998, 18: 4461-4472. PMID: 9614223, PMCID: PMC6792706, DOI: 10.1523/jneurosci.18-12-04461.1998.Peer-Reviewed Original ResearchConceptsBeta2-/- miceElectrophysiological experimentsBrain regionsNeuronal nicotinic acetylcholine receptor subunitBrain nicotinic receptorsNicotinic acetylcholine receptor subunitsMost brain regionsPatch-clamp recordingsReceptor autoradiography studiesOrder of potencyDifferent brain areasAcetylcholine receptor subunitsThin brain slicesDifferent brain regionsIndividual alpha subunitsAutoradiography studiesBrain slicesNicotinic receptorsNicotinic agonistsHigh affinitySubunit compositionBrain areasAlpha subunitAlpha7 subunitType 2