2025
Reduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease
Abulimiti A, Bae H, Ali A, Balakrishnan S, Tsujishita M, Gveric D, Tierney T, Jonas E, Smith P, Gentleman S, Alavian K. Reduced DJ-1-F1Fo ATP synthase association correlates with midbrain dopaminergic neuron vulnerability in idiopathic Parkinson’s disease. Science Advances 2025, 11: eads3051. PMID: 40479058, PMCID: PMC12143374, DOI: 10.1126/sciadv.ads3051.Peer-Reviewed Original ResearchConceptsProximity ligation assayVentral tegmental areaF1Fo-ATP synthaseProximity ligation assay signalsMetabolic efficiencyVentral tegmental area neuronsMitochondrial metabolic efficiencyProtein productionLigation assayMitochondrial activityMetabolic homeostasisIntracellular compartmentsMitochondrial efficiencyDistal neuritesParkinson's diseaseControl postmortem brainsImpaired mitochondrial efficiencySubstantia nigra pars compactaDopaminergic neuron vulnerabilityMesDA neuronsMesencephalic dopaminergicNeuronal vulnerabilityTegmental areaNeuronal subpopulationsIdiopathic Parkinson's diseaseDiminished reward circuit response underlies pain avoidance learning deficits in problem drinkers
Le T, Oba T, Li C. Diminished reward circuit response underlies pain avoidance learning deficits in problem drinkers. NeuroImage Clinical 2025, 45: 103762. PMID: 40009903, PMCID: PMC11908557, DOI: 10.1016/j.nicl.2025.103762.Peer-Reviewed Original ResearchConceptsPosterior cingulate cortexAvoidance learningReward circuitDrinking severityReward deficiencyLearning deficitsPain avoidanceProblem drinkersAlcohol useAvoidance learning deficitMedial orbitofrontal cortexReward circuit dysfunctionVentral tegmental areaPoor avoidance learningAssociated with problem drinkingOrbitofrontal cortexTegmental areaGo/NoGo taskCingulate cortexNeural correlatesBehavioral findingsCircuit dysfunctionAdult drinkersBrain regionsNeural processes
2024
Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release
Zhou X, Stine C, Prada P, Fusca D, Assoumou K, Dernic J, Bhat M, Achanta A, Johnson J, Pasqualini A, Jadhav S, Bauder C, Steuernagel L, Ravotto L, Benke D, Weber B, Suko A, Palmiter R, Stoeber M, Kloppenburg P, Brüning J, Bruchas M, Patriarchi T. Development of a genetically encoded sensor for probing endogenous nociceptin opioid peptide release. Nature Communications 2024, 15: 5353. PMID: 38918403, PMCID: PMC11199706, DOI: 10.1038/s41467-024-49712-0.Peer-Reviewed Original ResearchConceptsOpioid peptide releaseVentral tegmental areaAcute brain slicesN/OFQ actionsChemogenetic activationIn vivo studiesNociceptin/orphanin FQTegmental areaFibre photometryOpioid peptidesBrain slicesPharmacological profileGenetically encoded sensorIntracellular signal transducersReceptor ligandsPeptide releaseMammalian brainFunctional relevanceNeuronsBehavioral processesSignal transducerReleasePotential interactionsRegulatory functionsN/OFQ
2023
Ventral Tegmental Area M5 Muscarinic Receptors Mediate Effort-Choice Responding and Nucleus Accumbens Dopamine in a Sex-Specific Manner
Nunes E, Kebede N, Haight J, Foster D, Lindsley C, Conn P, Addy N. Ventral Tegmental Area M5 Muscarinic Receptors Mediate Effort-Choice Responding and Nucleus Accumbens Dopamine in a Sex-Specific Manner . Journal Of Pharmacology And Experimental Therapeutics 2023, 385: 146-156. PMID: 36828630, PMCID: PMC10108441, DOI: 10.1124/jpet.122.001438.Peer-Reviewed Original ResearchConceptsNucleus accumbens coreVentral tegmental areaM5 receptorsDA releaseMale ratsVTA infusionsDepressive disorderNucleus accumbensMuscarinic M5 receptorsSelective negative allosteric modulatorM5 muscarinic receptorsNegative allosteric modulatorsEffort-related choicePhasic DA releasePotential sex differencesSex-specific mannerACh toneVTA administrationCholinergic effectsMuscarinic receptorsFemale ratsTegmental areaPreclinical modelsDopamine releaseTherapeutic target
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 activityAgRP neurons control structure and function of the medial prefrontal cortex
Stutz B, Waterson MJ, Šestan-Peša M, Dietrich MO, Škarica M, Sestan N, Racz B, Magyar A, Sotonyi P, Liu ZW, Gao XB, Matyas F, Stoiljkovic M, Horvath TL. AgRP neurons control structure and function of the medial prefrontal cortex. Molecular Psychiatry 2022, 27: 3951-3960. PMID: 35906488, PMCID: PMC9891653, DOI: 10.1038/s41380-022-01691-8.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAgRP neuronsNon-selective dopamine receptor antagonistBrain functionPrefrontal cortexHypothalamic AgRP neuronsMedial thalamic neuronsAdministration of clozapineDopamine receptor antagonistVentral tegmental areaOscillatory network activityHigher-order brain functionsHypothalamic agoutiThalamic neuronsChemogenetic inhibitionDopaminergic neuronsReceptor antagonistTegmental areaNeuronal pathwaysSensorimotor gatingAdult miceModulatory impactAmbulatory behaviorConstitutive impairmentNeuronsBrain-wide electrical dynamics encode individual appetitive social behavior
Mague SD, Talbot A, Blount C, Walder-Christensen KK, Duffney LJ, Adamson E, Bey AL, Ndubuizu N, Thomas GE, Hughes DN, Grossman Y, Hultman R, Sinha S, Fink AM, Gallagher NM, Fisher RL, Jiang YH, Carlson DE, Dzirasa K. Brain-wide electrical dynamics encode individual appetitive social behavior. Neuron 2022, 110: 1728-1741.e7. PMID: 35294900, PMCID: PMC9126093, DOI: 10.1016/j.neuron.2022.02.016.Peer-Reviewed Original Research
2021
Sex Differences in the Ventral Tegmental Area and Nucleus Accumbens Proteome at Baseline and Following Nicotine Exposure
Lee AM, Mansuri MS, Wilson RS, Lam TT, Nairn AC, Picciotto MR. Sex Differences in the Ventral Tegmental Area and Nucleus Accumbens Proteome at Baseline and Following Nicotine Exposure. Frontiers In Molecular Neuroscience 2021, 14: 657064. PMID: 34335180, PMCID: PMC8317211, DOI: 10.3389/fnmol.2021.657064.Peer-Reviewed Original ResearchVentral tegmental areaC3H/HeJ miceGlial fibrillary acidic proteinChronic nicotine administrationNicotine administrationProtein abundanceProteomeIsobaric labelingNicotine exposureFemale miceTegmental areaHeJ miceNucleus accumbensNicotine addictionProteinSex differencesSample fractionationPathwayFibrillary acidic proteinTandem mass spectrometryNetwork analysisMouse strainsChronic nicotineMesolimbic systemNicotine reward
2020
Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats
Nunes EJ, Rupprecht LE, Foster DJ, Lindsley CW, Conn PJ, Addy NA. Examining the role of muscarinic M5 receptors in VTA cholinergic modulation of depressive-like and anxiety-related behaviors in rats. Neuropharmacology 2020, 171: 108089. PMID: 32268153, PMCID: PMC7313677, DOI: 10.1016/j.neuropharm.2020.108089.Peer-Reviewed Original ResearchConceptsSucrose preference testVentral tegmental areaMuscarinic M5 receptorsCholinergic toneM5 receptorsBehavioral effectsFemale ratsDepressive-like behavioral effectsIntra-VTA infusionAnxiogenic-like effectsAcetylcholinesterase inhibitor physostigmineAnxiety-related behaviorVTA administrationCholinergic modulationCholinergic receptorsMuscarinic receptorsInhibitor physostigmineSwim testTegmental areaMale ratsMood disordersVTA infusionsFST behaviorRatsPhysostigmine
2019
Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder
Pizzagalli D, Berretta S, Wooten D, Goer F, Pilobello K, Kumar P, Murray L, Beltzer M, Boyer-Boiteau A, Alpert N, Fakhri G, Mechawar N, Vitaliano G, Turecki G, Normandin M. Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder. JAMA Psychiatry 2019, 76: 854-861. PMID: 31042280, PMCID: PMC6495358, DOI: 10.1001/jamapsychiatry.2019.0801.Peer-Reviewed Original ResearchConceptsMajor depressive disorderDA transporter availabilityVentral tegmental areaDA transporterDAT availabilityTegmental areaDepressive disorderDA signalingPositron emission tomographyDAT expressionMcLean HospitalHealthy controlsMajor depressive disorder groupsNumbers of depressive episodesStriatal dopamine transporter bindingDA transporter levelsLevels of DAT expressionStriatal DAT expressionStriatal DAT availabilityDA transporter densityDAT binding potentialDopamine transporter bindingOlder healthy controlsMesolimbic pathwayDA clearance
2018
Granulocyte-Colony-Stimulating Factor Alters the Proteomic Landscape of the Ventral Tegmental Area
Mervosh NL, Wilson R, Rauniyar N, Hofford RS, Kutlu MG, Calipari ES, Lam TT, Kiraly DD. Granulocyte-Colony-Stimulating Factor Alters the Proteomic Landscape of the Ventral Tegmental Area. Proteomes 2018, 6: 35. PMID: 30249060, PMCID: PMC6313867, DOI: 10.3390/proteomes6040035.Peer-Reviewed Original ResearchGranulocyte-colony stimulating factorVentral tegmental areaTegmental areaG-CSF treatmentLimbic brain regionsCombination of cocaineMesolimbic dopamine circuitG-CSF functionInjection of cocaineStudy miceAvailable pharmacotherapiesAberrant plasticityDopamine releaseTreatment groupsSynaptic plasticityDopamine circuitsNeuronal morphologyBrain regionsSoluble cytokinesGranulocyte colonyCocaine addictionBrain functionStimulating factorProtein expressionSignificant tollGIRK 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 inhibitionGIRKThe L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathway
Addy NA, Nunes EJ, Hughley SM, Small KM, Baracz SJ, Haight JL, Rajadhyaksha AM. The L-type calcium channel blocker, isradipine, attenuates cue-induced cocaine-seeking by enhancing dopaminergic activity in the ventral tegmental area to nucleus accumbens pathway. Neuropsychopharmacology 2018, 43: 2361-2372. PMID: 29773910, PMCID: PMC6180103, DOI: 10.1038/s41386-018-0080-2.Peer-Reviewed Original ResearchConceptsL-type calcium channelsCocaine relapseLever depressionVentral tegmental areaCocaine self-administration trainingOriginal training contextLight cue presentationSelf-administration trainingSubjective effectsCocaine-seeking behaviorTegmental areaBehavioral effectsCocaine's subjective effectsL-type calcium channel blockerCue presentationMale Sprague-Dawley ratsTraining contextCocaine cuesNucleus accumbens coreNatural rewardsDA receptor activationCalcium channel blockersSprague-Dawley ratsPhasic dopaminePotential therapeutic targetAdolescent Nicotine Exposure Alters GABAA Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration
Thomas A, Ostroumov A, Kimmey B, Taormina M, Holden W, Kim K, Brown-Mangum T, Dani J. Adolescent Nicotine Exposure Alters GABAA Receptor Signaling in the Ventral Tegmental Area and Increases Adult Ethanol Self-Administration. Cell Reports 2018, 23: 68-77. PMID: 29617674, PMCID: PMC5983379, DOI: 10.1016/j.celrep.2018.03.030.Peer-Reviewed Original ResearchConceptsVentral tegmental areaAdolescent nicotine exposureNicotine exposureTegmental areaChloride extrusionLateral ventral tegmental areaSubsequent ethanol intakeVTA GABA neuronsNicotine-treated animalsGlucocorticoid receptor activationGABAA Receptor SignalingEthanol Self‐AdministrationGABA neuronsPathological drinkingVTA GABAAlcohol drinkingEthanol intakeReceptor activationSelf-AdministrationRisk profileGABANeuron responsesAdolescent smokingReceptor signalingReversal potential
2016
Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO
Gaiser EC, Gallezot JD, Worhunsky PD, Jastreboff AM, Pittman B, Kantrovitz L, Angarita GA, Cosgrove KP, Potenza MN, Malison RT, Carson RE, Matuskey D. Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO. Neuropsychopharmacology 2016, 41: 3042-3050. PMID: 27374277, PMCID: PMC5101552, DOI: 10.1038/npp.2016.115.Peer-Reviewed Original ResearchConceptsBody mass indexVentral striatumObese individualsD2/3R availabilityOB individualsReward regionsSubstantia nigra/ventral tegmental areaDopamine D2/3 receptor availabilityNormal-weight individualsTreatment of obesityVentral tegmental areaNovel pharmacologic targetsD2/3 receptor availabilitySN/VTAAgonist tracersOverweight cohortMass indexWeight individualsTegmental areaBrain reward regionsAntagonist tracersPharmacologic targetReceptor availabilitySecondary analysisNW individualsA Role for the GIRK3 Subunit in Methamphetamine-Induced Attenuation of GABAB Receptor-Activated GIRK Currents in VTA Dopamine Neurons
Munoz M, Padgett C, Rifkin R, Terunuma M, Wickman K, Contet C, Moss S, Slesinger P. A Role for the GIRK3 Subunit in Methamphetamine-Induced Attenuation of GABAB Receptor-Activated GIRK Currents in VTA Dopamine Neurons. Journal Of Neuroscience 2016, 36: 3106-3114. PMID: 26985023, PMCID: PMC4792929, DOI: 10.1523/jneurosci.1327-15.2016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBaclofenDopamine AgentsDopaminergic NeuronsFemaleG Protein-Coupled Inwardly-Rectifying Potassium ChannelsGABA-B Receptor AgonistsHomeodomain ProteinsIn Vitro TechniquesMaleMembrane PotentialsMethamphetamineMiceMice, Inbred C57BLMice, TransgenicReceptors, GABA-BTime FactorsTranscription FactorsTyrosine 3-MonooxygenaseVentral Tegmental AreaConceptsVentral tegmental area DA neuronsVentral tegmental areaExposure to psychostimulantsDA neuronsGIRK3 subunitsVentral tegmental area dopamine neuronsRepeated exposure to psychostimulantsExposure to addictive drugsExcitation of DA neuronsGABAB receptorsReward neural circuitryMesolimbic dopamine systemG-protein-gated inwardly rectifying potassiumGIRK currentsLocomotor sensitizationMesocorticolimbic dopamineMethamphetamine-inducedPsychostimulant exposureReward circuitDopamine systemReward pathwayTegmental areaD1R-likeAddictive drugsAddictive behaviorsAge-related changes in binding of the D2/3 receptor radioligand [11C](+)PHNO in healthy volunteers
Matuskey D, Worhunksy P, Correa E, Pittman B, Gallezot JD, Nabulsi N, Ropchan J, Sreeram V, Gudepu R, Gaiser E, Cosgrove K, Ding YS, Potenza MN, Huang Y, Malison RT, Carson RE. Age-related changes in binding of the D2/3 receptor radioligand [11C](+)PHNO in healthy volunteers. NeuroImage 2016, 130: 241-247. PMID: 26876475, PMCID: PMC4808424, DOI: 10.1016/j.neuroimage.2016.02.002.Peer-Reviewed Original ResearchConceptsPositron emission tomographyReceptor availabilitySN/VTADopamine systemMidbrain regionsSubstantia nigra/ventral tegmental areaHealthy control subjectsWhole-brain voxel-wise analysisVentral tegmental areaPrevious imaging studiesVoxel-wise analysisAge-associated declineAge-related changesAntagonist radiotracersExtrastriatal areasReference tissue modelAgonist radiotracerAge-related declineControl subjectsTegmental areaHealthy subjectsHealthy volunteersPositive correlationReceptor radioligandSecondary analysis
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 effectsCuesNeuroanatomic Differences Associated With Stress Susceptibility and Resilience
Anacker C, Scholz J, O’Donnell K, Allemang-Grand R, Diorio J, Bagot RC, Nestler EJ, Hen R, Lerch JP, Meaney MJ. Neuroanatomic Differences Associated With Stress Susceptibility and Resilience. Biological Psychiatry 2015, 79: 840-849. PMID: 26422005, PMCID: PMC5885767, DOI: 10.1016/j.biopsych.2015.08.009.Peer-Reviewed Original ResearchConceptsVentral tegmental areaMagnetic resonance imagingBrain regionsHippocampal CA3Resilient miceAnatomic differencesResonance imagingNeuroanatomic differencesStructural covarianceStructural magnetic resonance imagingSocial defeat stressLocal brain volumeT2-weighted sequencesDiffusion tensor imagingStress susceptibilitySocial avoidanceC57BL/6 miceControl miceStria terminalsRaphe nucleusPeriaqueductal grayTegmental areaBed nucleusDefeat stressNucleus accumbensA preliminary study of dopamine D2/3 receptor availability and social status in healthy and cocaine dependent humans imaged with [11C](+)PHNO
Matuskey D, Gaiser EC, Gallezot JD, Angarita GA, Pittman B, Nabulsi N, Ropchan J, MaCleod P, Cosgrove KP, Ding YS, Potenza MN, Carson RE, Malison RT. A preliminary study of dopamine D2/3 receptor availability and social status in healthy and cocaine dependent humans imaged with [11C](+)PHNO. Drug And Alcohol Dependence 2015, 154: 167-173. PMID: 26164205, PMCID: PMC4536182, DOI: 10.1016/j.drugalcdep.2015.06.039.Peer-Reviewed Original ResearchConceptsPositron emission tomographyNon-human primatesInverse associationCD groupReceptor availabilityHealthy non-human primatesSubstantia nigra/ventral tegmental areaBarratt Simplified MeasureDopamine D2/3 receptor availabilityBody mass indexVentral tegmental areaCocaine-dependent humansChronic cocaine administrationDependent humansD2/3 receptor availabilitySN/VTAMass indexCD subjectsRegional brainExtrastriatal regionsTegmental areaCocaine administrationAntagonist radioligandAgonist radioligandCD individuals
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