2025
Hypothesizing glucagon-like peptide 1 (GLP-1), agonists promote hypodopaminergia, resulting in heightened addictive reward-seeking and altered mood: Breaking the bubble and adding salt to a wound
Blum K, Dennen C, Lewandrowski K, Sharafshah A, Pinhasov A, Bowirrat A, Elman I, Cadet J, Braverman E, Thanos P, Makale M, Baron D, Ashford J, Fuehrlein B, Avena N, Gardner E, Badgaiyan R, Gondré—Lewis M, Modestino E, Khalsa J, Murphy K, Sunder K, Foojan Z, Jafari N, Carney P, Cortes R, Edwards D, Roy A, Smith D, Gold M. Hypothesizing glucagon-like peptide 1 (GLP-1), agonists promote hypodopaminergia, resulting in heightened addictive reward-seeking and altered mood: Breaking the bubble and adding salt to a wound. Medical Hypotheses 2025, 198: 111612. DOI: 10.1016/j.mehy.2025.111612.Peer-Reviewed Original ResearchReceptor agonistsGLP-1 receptor agonistsUse disorderGABA neuronsActivation of VTA GABA neuronsActivity of VTA dopamine neuronsIn vivo fiber photometryAttenuated cocaine seekingVTA dopamine neuronsVTA GABA neuronsReward-seeking behaviorAssociated with increased activityDopaminergic reward pathwayAlcohol use disorderSubstance use disordersGLP-1Cocaine seekingFluorescence in situ hybridizationReward-seekingReward pathwayAntiaddictive propertiesDopamine signalingDopaminergic pathwaysDopamine neuronsFiber photometryContextual cues facilitate dynamic value encoding in the mesolimbic dopamine system
Fraser K, Collins V, Wolff A, Ottenheimer D, Bornhoft K, Pat F, Chen B, Janak P, Saunders B. Contextual cues facilitate dynamic value encoding in the mesolimbic dopamine system. Current Biology 2025, 35: 746-760.e5. PMID: 39855205, PMCID: PMC11859769, DOI: 10.1016/j.cub.2024.12.031.Peer-Reviewed Original ResearchConceptsMesolimbic dopamine systemConditioned stimulusDopamine systemNucleus accumbensDopamine functionDopamine releaseOccasion setterDopamine neuronsActivity of ventral tegmental area dopamine neuronsVentral tegmental area dopamine neuronsTheory of dopamine functionNon-overlapping presentationSucrose deliverySucrose rewardContextual cuesBehavioral outputAdaptive behaviorDynamic environmental contextBehavioral responsesFemale ratsAccumbensStimuliSeeking behaviorDopamineMotor control
2023
Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease
Dong X, Bai Y, Liao Z, Gritsch D, Liu X, Wang T, Borges-Monroy R, Ehrlich A, Serrano G, Feany M, Beach T, Scherzer C. Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease. Nature Communications 2023, 14: 5327. PMID: 37723137, PMCID: PMC10507039, DOI: 10.1038/s41467-023-40348-0.Peer-Reviewed Original ResearchConceptsAlzheimer Disease-associated geneNon-neuronal cellsDisease-associated genesCircular RNAsNeuronal identityDisease neuropathologyAutism-associated genesParkinsonism genesHuman neuropsychiatric diseasesCell identityParkinson's disease neuropathologyGenesNeuropsychiatric diseasesRNALaser captureHuman brainIdentity of dopamineCircRNAsCellsPyramidal neuronsBrain cellsSynaptic specializationsDopamine neuronsDopamineNeuronsOperant Training for Highly Palatable Food Alters Translating Messenger RNA in Nucleus Accumbens D2 Neurons and Reveals a Modulatory Role of Ncdn
Montalban E, Giralt A, Taing L, Nakamura Y, Pelosi A, Brown M, de Pins B, Valjent E, Martin M, Nairn A, Greengard P, Flajolet M, Hervé D, Gambardella N, Roussarie J, Girault J. Operant Training for Highly Palatable Food Alters Translating Messenger RNA in Nucleus Accumbens D2 Neurons and Reveals a Modulatory Role of Ncdn. Biological Psychiatry 2023, 95: 926-937. PMID: 37579933, PMCID: PMC11059129, DOI: 10.1016/j.biopsych.2023.08.006.Peer-Reviewed Original ResearchStriatal projection neuronsNucleus accumbensPalatable foodProjection neuronsNAc neuronsD2-striatal projection neuronsWild-type miceMessenger RNAConditioning-induced changesSpine densityDopamine neuronsDopamine receptorsDownregulated genesD2 neuronsModulatory roleNAc dopamineDopamine DFood altersCompensatory mechanismsRegular foodNeuronsFeeding behaviorBehavioral responsesMRNA alterationsMice
2022
L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities
Nunes E, Addy N. L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities. Neuropharmacology 2022, 224: 109336. PMID: 36414149, PMCID: PMC11215796, DOI: 10.1016/j.neuropharm.2022.109336.Peer-Reviewed Original ResearchConceptsL-type calcium channelsVentral tegmental areaPre-clinical modelsTegmental areaSubstance useLTCC blockersMood disordersCalcium channelsCo-morbid psychiatric diagnosesDA neuronal activityVoltage-gated calcium channelsMood-related behaviorsSubstance use disordersCalcium channel regulationStress-induced plasticityAccumbens pathwayCardiac medicationsDopamine neuronsLTCC subtypesNeuronal activityNeuronal firingUse disordersPsychiatric diagnosisCalcium entryDopamine activityA hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice
Korchynska S, Rebernik P, Pende M, Boi L, Alpár A, Tasan R, Becker K, Balueva K, Saghafi S, Wulff P, Horvath TL, Fisone G, Dodt HU, Hökfelt T, Harkany T, Romanov RA. A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice. Nature Communications 2022, 13: 5944. PMID: 36209152, PMCID: PMC9547883, DOI: 10.1038/s41467-022-33584-3.Peer-Reviewed Original ResearchConceptsLateral septumDopamine neuronsSuprachiasmatic nucleusSomatostatin-containing neuronsStimulation ex vivoAmphetamine-induced hyperlocomotionRegulation of locomotionDopamine outputChemogenetic inhibitionNeuropeptidergic innervationPeriventricular nucleusChemogenetic manipulationHypothalamic lociSynaptic targetsAnterior subdivisionEx vivoBrain clockNeuronsSedentary periodL activityHyperlocomotionCellular targetsMicePeVNInnervation
2020
Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo
Hiller B, Marmion D, Gross R, Thompson C, Chavez C, Brundin P, Wakeman D, McMahon C, Kordower J. Mitomycin-C treatment during differentiation of induced pluripotent stem cell-derived dopamine neurons reduces proliferation without compromising survival or function in vivo. Stem Cells Translational Medicine 2020, 10: 278-290. PMID: 32997443, PMCID: PMC7848297, DOI: 10.1002/sctm.20-0014.Peer-Reviewed Original ResearchConceptsDopamine neuronsInduced pluripotent stem cellsParkinson's diseaseStem cell-derived dopamine neuronsPD cell therapyMidbrain dopamine neuronsLong-term survivalTransplant of cellsStem cellsHuman induced pluripotent stem cellsPluripotent stem cellsNeuron preparationsMitomycin C treatmentAthymic ratsDrug selectionUndesirable proliferationCell therapyRobust survivalLower proliferationVivo functionNeuronsTransplantationSurvivalProliferative cellsDiseaseGeneration of Pluripotent Stem Cells Using Somatic Cell Nuclear Transfer and Induced Pluripotent Somatic Cells from African Green Monkeys
Chung YG, Seay M, Elsworth J, Redmond D. Generation of Pluripotent Stem Cells Using Somatic Cell Nuclear Transfer and Induced Pluripotent Somatic Cells from African Green Monkeys. Stem Cells And Development 2020, 29: 1294-1307. PMID: 32715987, DOI: 10.1089/scd.2020.0059.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell LineChlorocebus aethiopsChromosome BandingCloning, OrganismCulture MediaCytogenetic AnalysisDNADopaminergic NeuronsEmbryonic DevelopmentEmbryonic Stem CellsFemaleGenotypeHumansInduced Pluripotent Stem CellsMitochondriaNuclear Transfer TechniquesOvaryTyrosine 3-MonooxygenaseConceptsAfrican green monkeysInduced pluripotent stem cellsCell linesGreen monkeysStem cellsEffective cell replacement therapyPromising potential therapyPluripotent stem cellsDopamine depletionReplacement therapyDopamine neuronsCell replacement therapyBrain pathologyDonor monkeyParkinson's diseasePotential therapyMonkey studiesFemale monkeysClinical predictive powerImmune rejectionImmune systemAccidental exposurePossible treatmentIPSC linesRodent experimentsSynaptic Changes in Parkinson Disease Assessed with in vivo Imaging
Matuskey D, Tinaz S, Wilcox KC, Naganawa M, Toyonaga T, Dias M, Henry S, Pittman B, Ropchan J, Nabulsi N, Suridjan I, Comley RA, Huang Y, Finnema SJ, Carson RE. Synaptic Changes in Parkinson Disease Assessed with in vivo Imaging. Annals Of Neurology 2020, 87: 329-338. PMID: 31953875, PMCID: PMC7065227, DOI: 10.1002/ana.25682.Peer-Reviewed Original ResearchConceptsSubstantia nigraParkinson's diseaseNormal controlsSynaptic changesPositron emission tomographic imagingSynaptic vesicle glycoprotein 2AParkinson's disease groupParkinson's disease subjectsEmission tomographic imagingPrimary brain areasAnn NeurolPostmortem autoradiographyBilateral diseaseNonmotor symptomsSynaptic lossNeuronal alterationsRelevant cortical areasStriatal dopamineBrainstem nucleiDisease groupDopamine neuronsLocus coeruleusCortical areasRed nucleusDopamine system
2019
Dopamine neuronal protection in the mouse Substantia nigra by GHSR is independent of electric activity
Stutz B, Nasrallah C, Nigro M, Curry D, Liu ZW, Gao XB, Elsworth JD, Mintz L, Horvath TL. Dopamine neuronal protection in the mouse Substantia nigra by GHSR is independent of electric activity. Molecular Metabolism 2019, 24: 120-138. PMID: 30833218, PMCID: PMC6531791, DOI: 10.1016/j.molmet.2019.02.005.Peer-Reviewed Original ResearchConceptsSN DA neuronsDA neuronsSubstantia nigraDA cellsDopamine outputNeuronal protectionNeuronal survivalParkinson's diseaseDA neuron survivalDA neuronal survivalDesigner drugs (DREADD) technologyNeuronal pacemaker activityElectrical activityMouse substantia nigraElectric activityNeuron electrical activityAnimal motor behaviorGhrelin activationGHSR activationTetrahydropyridine (MPTP) treatmentNeuroprotective factorsNeuron survivalDopamine neuronsGhrelin receptorExogenous administration
2018
Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
Dong X, Liao Z, Gritsch D, Hadzhiev Y, Bai Y, Locascio J, Guennewig B, Liu G, Blauwendraat C, Wang T, Adler C, Hedreen J, Faull R, Frosch M, Nelson P, Rizzu P, Cooper A, Heutink P, Beach T, Mattick J, Müller F, Scherzer C. Publisher Correction: Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nature Neuroscience 2018, 22: 144-147. PMID: 30482917, DOI: 10.1038/s41593-018-0277-z.Peer-Reviewed Original ResearchDopamine neuronsNeuropsychiatric diseasesGIRK currents in VTA dopamine neurons control the sensitivity of mice to cocaine-induced locomotor sensitization
Rifkin R, Huyghe D, Li X, Parakala M, Aisenberg E, Moss S, Slesinger P. GIRK currents in VTA dopamine neurons control the sensitivity of mice to cocaine-induced locomotor sensitization. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: e9479-e9488. PMID: 30228121, PMCID: PMC6176583, DOI: 10.1073/pnas.1807788115.Peer-Reviewed Original ResearchConceptsVentral tegmental areaVentral tegmental area dopamine neuronsCocaine-induced locomotor sensitizationDopamine neuronsLocomotor sensitizationVTA dopamine neuronsSubstantia nigra pars compactaGIRK currentsG-protein-gated inwardly rectifying potassium channelsCocaine addictionReward circuitTegmental areaGIRK channelsEndosomal adaptor proteinTreat addictionGIRK3 subunitsNeural circuitsInwardly rectifying potassium channelsRectifying potassium channelsDopamineGABAAddictionSpike firingSource of inhibitionGIRKEnhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease
Dong X, Liao Z, Gritsch D, Hadzhiev Y, Bai Y, Locascio J, Guennewig B, Liu G, Blauwendraat C, Wang T, Adler C, Hedreen J, Faull R, Frosch M, Nelson P, Rizzu P, Cooper A, Heutink P, Beach T, Mattick J, Müller F, Scherzer C. Enhancers active in dopamine neurons are a primary link between genetic variation and neuropsychiatric disease. Nature Neuroscience 2018, 21: 1482-1492. PMID: 30224808, PMCID: PMC6334654, DOI: 10.1038/s41593-018-0223-0.Peer-Reviewed Original ResearchConceptsExpression quantitative trait loci analysisQuantitative trait loci analysisDopamine neuronsGenetic variants associated with schizophreniaDisease-Associated VariantsVariants associated with schizophreniaNoncoding elementsCis-regulationEnhancer RNAsGenetic variationNeuropsychiatric traitsLocus analysisRegulatory mechanismsActivity in situDNA logic gatesSpecialized functionsNeuropsychiatric diseasesActivity enhancementDopamineMouse brainHuman brainExpressionChromosomeNeuronsParkinson's diseaseα1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice
Zhang H, Chaudhury D, Nectow AR, Friedman AK, Zhang S, Juarez B, Liu H, Pfau ML, Aleyasin H, Jiang C, Crumiller M, Calipari ES, Ku SM, Morel C, Tzavaras N, Montgomery SE, He M, Salton SR, Russo SJ, Nestler EJ, Friedman JM, Cao JL, Han MH. α1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice. Biological Psychiatry 2018, 85: 226-236. PMID: 30336931, PMCID: PMC6800029, DOI: 10.1016/j.biopsych.2018.08.020.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AgonistsAdrenergic alpha-1 Receptor AntagonistsAdrenergic beta-3 Receptor AgonistsAdrenergic beta-3 Receptor AntagonistsAnimalsBehavior, AnimalDopaminergic NeuronsHomeostasisLocus CoeruleusMaleMiceNeural PathwaysNeuronal PlasticityReceptors, Adrenergic, alpha-1Receptors, Adrenergic, beta-3Resilience, PsychologicalStress, PsychologicalVentral Tegmental AreaConceptsSocial defeat stressDA neuronsSusceptible miceHomeostatic plasticityLocus coeruleusDefeat stressAdrenergic receptorsChronic social defeat stress (CSDS) modelSocial defeat stress modelVTA DA neuronsDepression-related behaviorsMesolimbic DA neuronsMesolimbic dopamine neuronsΒ3-adrenergic receptorMolecular profiling studiesNew molecular targetsSocial stressCircuit neuronsLC neuronsDopamine neuronsNucleus accumbensOptogenetic activationCellular hyperactivityPrecise circuitryStress resilienceLoss of glutamate signaling from the thalamus to dorsal striatum impairs motor function and slows the execution of learned behaviors
Melief EJ, McKinley JW, Lam JY, Whiteley NM, Gibson AW, Neumaier JF, Henschen CW, Palmiter RD, Bamford NS, Darvas M. Loss of glutamate signaling from the thalamus to dorsal striatum impairs motor function and slows the execution of learned behaviors. Npj Parkinson's Disease 2018, 4: 23. PMID: 30083593, PMCID: PMC6072777, DOI: 10.1038/s41531-018-0060-6.Peer-Reviewed Original ResearchParkinson's diseaseCentral lateralDopamine neuronsMotor functionDorsal striatumMajor projection fieldBeam-walking testImpairs motor functionViral vector approachLewy body inclusionsMidbrain dopamine neuronsMotor coordination tasksMorris water mazeSlowness of thoughtLoss of glutamateTwo-way active avoidance taskGlutamatergic neuronsMotor abnormalitiesActive avoidance taskLox miceExcitatory inputsThalamic regionsWater mazeCognitive impairmentCell loss
2017
Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo
Wakeman D, Hiller B, Marmion D, McMahon C, Corbett G, Mangan K, Ma J, Little L, Xie Z, Perez-Rosello T, Guzman J, Surmeier D, Kordower J. Cryopreservation Maintains Functionality of Human iPSC Dopamine Neurons and Rescues Parkinsonian Phenotypes In Vivo. Stem Cell Reports 2017, 9: 149-161. PMID: 28579395, PMCID: PMC5511045, DOI: 10.1016/j.stemcr.2017.04.033.Peer-Reviewed Original ResearchConceptsParkinson's diseaseDopamine neuronsMidbrain dopamine neuronsStem cell therapyGrafted neuronsHost striatumCell-based therapiesPluripotent stem cell therapyFunctional deficitsPrimate modelFiber innervationParkinsonian phenotypeTherapeutic efficacyTransplantation studiesCell therapyNeuronsSignificant reversalTranslational developmentBehavioral assessmentClinical applicationTherapyElectrophysiological signaturesRatsDiseaseMinimal manipulationRegulator of G‐protein signaling 6 (RGS6) expression in human substantia nigra pars compacta (SNc) and loss in Parkinson's disease (PD)
Luo Z, Ahlers K, Yang J, Chakravarti B, Stevens H, Narayanan N, Fisher R. Regulator of G‐protein signaling 6 (RGS6) expression in human substantia nigra pars compacta (SNc) and loss in Parkinson's disease (PD). The FASEB Journal 2017, 31 DOI: 10.1096/fasebj.31.1_supplement.659.23.Peer-Reviewed Original ResearchSubstantia nigra pars compactaSNc DA neuronsDA neuronsParkinson's diseasePD patientsHuman substantia nigra pars compactaPotential novel therapeutic targetCritical neuroprotective roleDA neuron degenerationTyrosine hydroxylase expressionNovel therapeutic targetDevastating neurodegenerative disorderAge-dependent lossSNc neuronsMotor deficitsNeuroprotective rolePars compactaPathogenic linkNeuron degenerationPD treatmentDopamine neuronsHydroxylase expressionBehavioral deficitsDA contentImmunohistochemical analysis
2016
Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes
Romanov RA, Zeisel A, Bakker J, Girach F, Hellysaz A, Tomer R, Alpár A, Mulder J, Clotman F, Keimpema E, Hsueh B, Crow AK, Martens H, Schwindling C, Calvigioni D, Bains JS, Máté Z, Szabó G, Yanagawa Y, Zhang MD, Rendeiro A, Farlik M, Uhlén M, Wulff P, Bock C, Broberger C, Deisseroth K, Hökfelt T, Linnarsson S, Horvath TL, Harkany T. Molecular interrogation of hypothalamic organization reveals distinct dopamine neuronal subtypes. Nature Neuroscience 2016, 20: 176-188. PMID: 27991900, PMCID: PMC7615022, DOI: 10.1038/nn.4462.Peer-Reviewed Original Research
2015
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi E, Hollander B, Farooq U, Vashchinkina E, Rajkumar R, Nutt D, Hyytiä P, Dawe G, Koulu M. Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse. Pharmacological Reviews 2015, 67: 872-1004. PMID: 26403687, DOI: 10.1124/pr.115.010967.Peer-Reviewed Original ResearchMeSH KeywordsAlcoholismalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic AcidAmphetaminesAnimalsBehavior, AddictiveBenzodiazepinesBrainCannabinoidsCocaineDepressionDose-Response Relationship, DrugGene ExpressionHallucinogensHumansIllicit DrugsNarcoticsNerve Growth FactorsNeuroimagingNeuronal PlasticityNicotineReceptors, N-Methyl-D-AspartateReceptors, NicotinicSubstance-Related DisordersSynaptic TransmissionConceptsDrugs of abuseAdolescent drug exposureStress-induced reinstatementBehavioral changesBrain processesDrug seekingCognitive alterationsRecreational drug usersAbuseNeuroplasticityNeuropsychiatric illnessAddictionVentral tegmental areaAppropriate responseAdministration of drugsRegion-specific changesBrain cell populationsMechanism of actionDrug intakeDopamine neuronsDrug exposureTegmental areaRelevant doseDrug effectsCues
2014
Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons
Mazei-Robison MS, Appasani R, Edwards S, Wee S, Taylor SR, Picciotto MR, Koob GF, Nestler EJ. Self-Administration of Ethanol, Cocaine, or Nicotine Does Not Decrease the Soma Size of Ventral Tegmental Area Dopamine Neurons. PLOS ONE 2014, 9: e95962. PMID: 24755634, PMCID: PMC3995955, DOI: 10.1371/journal.pone.0095962.Peer-Reviewed Original ResearchConceptsVentral tegmental areaSoma sizeDopamine neuronsVentral tegmental area dopamine neuronsChronic opiate administrationAdditional drug classesDrug-specific mannerMorphological changesSelf-administer cocaineOpiate administrationTegmental areaDrug classesDA circuitsMesolimbic DA circuitSelf-AdministrationFiring rateSimilar morphological changesGeneral hallmarkNeuronsNicotineCocaineDrugsRecent findingsPrevious observationsNeuroplasticity
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