2022
Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear
Lee B, Pothula S, Wu M, Kang H, Girgenti MJ, Picciotto MR, DiLeone RJ, Taylor JR, Duman RS. Positive modulation of N-methyl-D-aspartate receptors in the mPFC reduces the spontaneous recovery of fear. Molecular Psychiatry 2022, 27: 2580-2589. PMID: 35418600, PMCID: PMC9135632, DOI: 10.1038/s41380-022-01498-7.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderFear extinctionInfralimbic medial prefrontal cortexFear conditioning modelEnhanced fear extinctionFear-based behaviorsProlonged stress modelMedial prefrontal cortexSpontaneous recoveryIL-mPFCPTSD modelPTSD treatmentStress disorderPrefrontal cortexSPS modelN-methyl-D-aspartate receptor modulatorsBrain-derived neurotrophic factorN-methyl-D-aspartate receptorsBehavioral effectsIncreased attentionMPFCPreclinical findingsPyramidal neuronsNeurotrophic factorMale miceHippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs
Mineur YS, Mose TN, Vanopdenbosch L, Etherington IM, Ogbejesi C, Islam A, Pineda CM, Crouse RB, Zhou W, Thompson DC, Bentham MP, Picciotto MR. Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs. Molecular Psychiatry 2022, 27: 1829-1838. PMID: 34997190, PMCID: PMC9106825, DOI: 10.1038/s41380-021-01404-7.Peer-Reviewed Original ResearchConceptsStress-related behaviorsCholinergic inputMedial septum/diagonal bandBehavioral effectsBrain ACh levelsChAT-positive neuronsSelective chemogenetic activationMuscarinic ACh receptorsDepression-like symptomsSignificant behavioral effectsHippocampal acetylcholineMaladaptive behavioral responsesAntidepressant effectsCholinergic neuronsACh releaseChemogenetic activationChemogenetic inhibitionCholinergic antagonistsLocal infusionAcetylcholine levelsACh levelsDiagonal bandACh receptorsHippocampal neuronsPharmacological approaches
2020
Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons
Pothula S, Liu RJ, Wu M, Sliby AN, Picciotto MR, Banerjee P, Duman RS. Positive modulation of NMDA receptors by AGN-241751 exerts rapid antidepressant-like effects via excitatory neurons. Neuropsychopharmacology 2020, 46: 799-808. PMID: 33059355, PMCID: PMC8027594, DOI: 10.1038/s41386-020-00882-7.Peer-Reviewed Original ResearchConceptsAntidepressant-like effectsMedial prefrontal cortexRapid antidepressant-like effectsGluN2B-containing NMDARsPositive allosteric modulatorsNMDAR positive allosteric modulatorExcitatory neuronsExerts antidepressant-like effectsAntidepressant-like behavioral effectsPrefrontal cortexBehavioral effectsAkt/mTORAntidepressant-like actionChronic unpredictable stressNMDA receptor activityRecent preclinical studiesMajor depressive disorderSpecific knockdownParvalbumin inhibitory neuronsCellular triggersSynaptic proteinsGlutamatergic systemNMDAR activityClinical trialsDepressive disorder
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
2011
Reduced locomotor responses to cocaine in ghrelin-deficient mice
Abizaid A, Mineur YS, Roth RH, Elsworth JD, Sleeman MW, Picciotto MR, Horvath TL. Reduced locomotor responses to cocaine in ghrelin-deficient mice. Neuroscience 2011, 192: 500-506. PMID: 21699961, DOI: 10.1016/j.neuroscience.2011.06.001.Peer-Reviewed Original ResearchConceptsGhrelin KO miceWT miceDopamine releaseLocomotor activityBehavioral effectsDopamine metabolite concentrationsGhrelin-deficient miceLocomotor-stimulating effectsDopamine cell activityEffects of cocaineMesolimbic dopaminergic systemWild-type littermatesOrexigenic hormoneChronic injectionsDopamine utilizationDaily injectionsStriatal dopamineMesolimbic systemWT littermatesDopaminergic systemDaily cocaineFood intakeRewarding effectsPsychostimulant effectsLocomotor responseFACS Identifies Unique Cocaine-Induced Gene Regulation in Selectively Activated Adult Striatal Neurons
Guez-Barber D, Fanous S, Golden SA, Schrama R, Koya E, Stern AL, Bossert JM, Harvey BK, Picciotto MR, Hope BT. FACS Identifies Unique Cocaine-Induced Gene Regulation in Selectively Activated Adult Striatal Neurons. Journal Of Neuroscience 2011, 31: 4251-4259. PMID: 21411666, PMCID: PMC3073079, DOI: 10.1523/jneurosci.6195-10.2011.Peer-Reviewed Original ResearchConceptsStriatal neuronsFluorescence-activated cell sortingNeural activity marker FosCocaine-induced locomotionActivity marker FosAdult striatal neuronsUnique gene expression profileP38 MAPK signalingCell-type specificityGene expression profilesSmall proportionTransgenic ratsActivated neuronsImmediate early genesMolecular neuroadaptationsSpecific neuronsGene regulationBehavioral effectsNeuronsAbused drugsMAPK signalingExpression profilesProtein productsCocaineLacZ gene
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 ResearchConceptsDesensitization 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 effectsNAChRsDesensitization
2003
α4β2* Nicotinic Acetylcholine Receptors Modulate the Effects of Ethanol and Nicotine on the Acoustic Startle Response
Owens JC, Balogh SA, McClure‐Begley T, Butt CM, Labarca C, Lester HA, Picciotto MR, Wehner JM, Collins AC. α4β2* Nicotinic Acetylcholine Receptors Modulate the Effects of Ethanol and Nicotine on the Acoustic Startle Response. Alcohol Clinical And Experimental Research 2003, 27: 1867-1875. PMID: 14691373, DOI: 10.1097/01.alc.0000102700.72447.0f.Peer-Reviewed Original ResearchConceptsAcoustic startle responseEffects of ethanolLSxSS RIStartle responseAcoustic startleAlpha4beta2 nAChRsEthanol effectsBeta2 null mutant miceNeuronal nicotinic cholinergic receptorsEthanol-induced depressionNicotinic cholinergic receptorsPotential roleNicotinic acetylcholine receptorsNull mutant miceAlpha4 nAChRsCholinergic receptorsTobacco abuseNicotine effectsT polymorphismAcetylcholine receptorsLSXSS recombinantMutant miceBehavioral effectsNicotineStartleNicotine as a modulator of behavior: beyond the inverted U
Picciotto MR. Nicotine as a modulator of behavior: beyond the inverted U. Trends In Pharmacological Sciences 2003, 24: 493-499. PMID: 12967775, DOI: 10.1016/s0165-6147(03)00230-x.Peer-Reviewed Original ResearchConceptsNeuronal pathwaysEffects of nicotineNicotinic acetylcholine receptorsNeurotransmitter release studiesSmoking cessationNicotine reinforcementOccasional smokingKnockout mouse studiesSmoking behaviorAnimal studiesAcetylcholine receptorsDifferent subtypesMouse studiesBehavioral effectsNew interventionsNicotineElectrophysiological experimentsActivation stateRecent dataBehavioral responsesModulator of behaviorSmokingPathwaySubtypesReceptorsThe neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal
Zachariou V, Brunzell DH, Hawes J, Stedman DR, Bartfai T, Steiner RA, Wynick D, Langel Ü, Picciotto MR. The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 9028-9033. PMID: 12853567, PMCID: PMC166432, DOI: 10.1073/pnas.1533224100.Peer-Reviewed Original ResearchConceptsMorphine withdrawal signsWithdrawal signsOpiate withdrawalGalanin agonistsEffects of galaninLocus coeruleus neuronsC-Fos immunoreactivityBlood-brain barrierEndogenous galaninMorphine withdrawalNoradrenergic neuronsCoeruleus neuronsC57BL/6 miceNeurochemical signsNeuropeptide galaninLocus coeruleusPossible molecular mechanismsTyrosine hydroxylaseGalaninNeuronal activityGalanin peptidePhysical signsTransgenic miceDrug dependenceBehavioral effects
2002
Neuronal Systems Underlying Behaviors Related to Nicotine Addiction: Neural Circuits and Molecular Genetics
Picciotto MR, Corrigall WA. Neuronal Systems Underlying Behaviors Related to Nicotine Addiction: Neural Circuits and Molecular Genetics. Journal Of Neuroscience 2002, 22: 3338-3341. PMID: 11978809, PMCID: PMC6758396, DOI: 10.1523/jneurosci.22-09-03338.2002.Peer-Reviewed Original ResearchConceptsAction of nicotineNicotine addictionNicotinic acetylcholine receptor subunitsAcetylcholine receptor subunitsStudies of miceSerotonergic nucleiNicotine effectsDopaminergic activityDopaminergic systemNicotine dependenceBrainstem cholinergicNeural circuitsNeuronal systemsReceptor subunitsBehavioral effectsNicotineAddictionRecent studiesNeural systemsInitial observationsCholinergicGABAergicMolecular geneticsMice
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
2000
Nicotinic Receptors in the Brain: Links between Molecular Biology and Behavior
Picciotto M, Caldarone B, King S, Zachariou V. Nicotinic Receptors in the Brain: Links between Molecular Biology and Behavior. Neuropsychopharmacology 2000, 22: 451-465. PMID: 10731620, DOI: 10.1016/s0893-133x(99)00146-3.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNicotinic receptorsIndividual subunitsNicotinic receptor subtypesNicotinic receptor agonistsMolecular biologyNicotinic acetylcholine receptorsAcetylcholine receptor subunitsPain sensitivityReceptor agonistReceptor subtypesAnimal studiesNicotinic subunitsAcetylcholine receptorsAddictive propertiesMolecular cloningMolecular dataReceptor subunitsBehavioral effectsNicotineSubunit combinationsReceptorsNative receptorSubunitsSubunit compositionSubsequent studies
1999
Use of knock-out mice to determine the molecular basis for the actions of nicotine
Picciotto M, Zoli M, Changeux J. Use of knock-out mice to determine the molecular basis for the actions of nicotine. Nicotine & Tobacco Research 1999, 1: s121-s125. PMID: 11768168, DOI: 10.1080/14622299050011931.Peer-Reviewed Original ResearchConceptsElectrophysiological propertiesBehavioral effectsSubunit combinationsAction of nicotineDifferent neurotransmitter systemsEffects of nicotineMesolimbic dopamine systemIndividual receptor subtypesNicotinic acetylcholine receptorsBinding of nicotinePossible subunit combinationsDifferent subunit combinationsNicotine effectsNicotine receptorsNicotine reinforcementReceptor subtypesDopamine levelsNeurotransmitter systemsDopamine systemNicotinic subunitsAcetylcholine receptorsAddictive propertiesNicotineMiceBeta2 subunit
1997
Contribution of nicotinic acetylcholine receptors containing the β2-subunit to the behavioural effects of nicotine
Picciotto MR, Zoli M, Zachariou V, Changeux J. Contribution of nicotinic acetylcholine receptors containing the β2-subunit to the behavioural effects of nicotine. Biochemical Society Transactions 1997, 25: 824-829. PMID: 9388554, DOI: 10.1042/bst0250824.Peer-Reviewed Original Research