2001
Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease
Collier TJ, Sortwell CE, Elsworth JD, Taylor JR, Roth RH, Sladek JR, Redmond DE. Embryonic ventral mesencephalic grafts to the substantia nigra of MPTP‐treated monkeys: Feasibility relevant to multiple‐target grafting as a therapy for Parkinson's disease. The Journal Of Comparative Neurology 2001, 442: 320-330. PMID: 11793337, DOI: 10.1002/cne.10108.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBrain Tissue TransplantationCell DifferentiationChlorocebus aethiopsDopamineGraft SurvivalHomovanillic AcidImmunohistochemistryMaleNeostriatumNerve RegenerationNeuritesNeuronsParkinsonian DisordersRecovery of FunctionStem Cell TransplantationStem CellsSubstantia NigraTreatment OutcomeTyrosine 3-MonooxygenaseConceptsSubstantia nigraParkinson's diseaseDA neuronsVentral mesencephalonTyrosine hydroxylaseTH-positive fiber densityEmbryonic DA neuronsEmbryonic dopamine neuronsRostral substantia nigraStriatal DA depletionVentral mesencephalic graftsBasal ganglia circuitryBasal ganglia structuresSuboptimal therapeutic outcomesAfrican green monkeysDA modulationGrafted neuronsVM graftsMesencephalic graftsParkinsonian monkeysSN neuronsDA depletionReplacement therapyDA replacementDA levelsEffects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5
Bibb J, Chen J, Taylor J, Svenningsson P, Nishi A, Snyder G, Yan Z, Sagawa Z, Ouimet C, Nairn A, Nestler E, Greengard P. Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 2001, 410: 376-380. PMID: 11268215, DOI: 10.1038/35066591.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCocaineCocaine-Related DisordersCorpus StriatumCyclin-Dependent Kinase 5Cyclin-Dependent KinasesDopamineDopamine and cAMP-Regulated Phosphoprotein 32Enzyme InhibitorsGene Expression Regulation, EnzymologicKinetinMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsOligonucleotide Array Sequence AnalysisPhosphoproteinsPhosphorylationProto-Oncogene Proteins c-fosPsychomotor PerformancePurinesRatsRats, Sprague-DawleyReceptors, Dopamine D1RoscovitineSignal TransductionConceptsTranscription factorsSuch transcription factorsDownstream target genesCyclin-dependent kinase 5DNA array analysisTarget genesGene expressionCocaine administrationKinase 5Inducible transgenic miceChronic exposureCdk5 inhibitorMessenger RNACocaine addictionArray analysisDopamine-mediated neurotransmissionDopamine-containing nerve terminalsMedium spiny neuronsD1 dopamine receptorsChronic cocaine administrationOverexpression of ΔFosBProteinTransgenic miceAdaptive changesSpiny neurons
2000
Role for dopamine in the behavioral functions of the prefrontal corticostriatal system: implications for mental disorders and psychotropic drug action
Jentsch J, Roth R, Taylor J. Role for dopamine in the behavioral functions of the prefrontal corticostriatal system: implications for mental disorders and psychotropic drug action. Progress In Brain Research 2000, 126: 433-453. PMID: 11105661, DOI: 10.1016/s0079-6123(00)26028-7.Peer-Reviewed Original ResearchMeSH KeywordsAmphetaminesAmygdalaAnimalsBehaviorBrain MappingCentral Nervous System StimulantsCognitionCorpus StriatumDepressionDopamineDopamine AgonistsEmotionsHaplorhiniHumansLearningLimbic SystemMammalsMemoryMental DisordersNeural PathwaysNeurotransmitter AgentsNucleus AccumbensPhencyclidinePrefrontal CortexPsychotropic DrugsReceptors, NeurotransmitterRewardSchizophreniaSubstance-Related DisordersConceptsForebrain sitesPsychotropic drug actionPrecise anatomical sitesRole of dopamineDopaminergic dysfunctionDopaminergic transmissionDopaminergic functionDopamine neuronsDopaminergic responseReward-related stimuliCorticolimbic circuitsChronic activationDopaminergic activationStriatal regionsAfferent controlAnatomical sitesCorticostriatal systemMental disordersNeuropsychiatric disordersNeuromodulatory systemsPersistent neuroadaptationsDrug actionBehavioral functionsCellular mechanismsDopamine
1999
Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment
Elsworth J, Taylor J, Sladek J, Collier T, Redmond D, Roth R. Striatal dopaminergic correlates of stable parkinsonism and degree of recovery in old-world primates one year after MPTP treatment. Neuroscience 1999, 95: 399-408. PMID: 10658619, DOI: 10.1016/s0306-4522(99)00437-6.Peer-Reviewed Original ResearchConceptsHomovanillic acid/dopamine ratioMPTP treatmentStriatal dopamine levelsDopamine levelsDopamine lossDopamine depletionDopamine ratioStriatal subregionsNucleus accumbensCaudate nucleusDopamine concentrationsOne-yearSeverity categoriesDopamine neuron integrityVentromedial caudate nucleusStriatal dopamine lossHomovanillic acid concentrationsStriatal dopaminergic functionMarked increaseNormal motor performancePaucity of dataMetabolic activityNon-human primatesParkinsonian disabilityTetrahydropyridine (MPTP) modelImpulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli
Jentsch J, Taylor J. Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology 1999, 146: 373-390. PMID: 10550488, DOI: 10.1007/pl00005483.Peer-Reviewed Original ResearchConceptsControl of behaviorInhibitory controlIncentive learning processesDrug abuseInhibitory response controlReward-related stimuliDrug-seeking behaviorChronic drug useCognitive impulsivityMotivational processesRelated stimuliMotivational qualitiesFrontostriatal systemFrontostriatal dysfunctionDrug seekingDrugs of abuseNeuro-anatomicalVentral striatumDrive stateAllocation of behaviorAppropriate behavioral patternsCognitive dysfunctionResponse controlFrontal cortexPrimate brainSpontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys
Taylor J, Elsworth J, Lawrence M, Sladek J, Roth R, Redmond D. Spontaneous Blink Rates Correlate with Dopamine Levels in the Caudate Nucleus of MPTP-Treated Monkeys. Experimental Neurology 1999, 158: 214-220. PMID: 10448434, DOI: 10.1006/exnr.1999.7093.Peer-Reviewed Original ResearchConceptsCaudate nucleusConcentration of DAEye blink rateBlink rateDA ratioDopaminergic regulationD1 agonist dihydrexidineDA D2 receptorsDopaminergic neurotoxin MPTPSeverity of parkinsonismSpontaneous eye blink rateSpecific brain regionsAntiparkinsonian effectsDA depletionD2 agonistDopamine D1Dopamine levelsNeurotoxin MPTPD2 receptorsMPTPNormal animalsRostral portionSubcortical regionsBrain regionsVentromedial regionAltered frontal cortical dopaminergic transmission in monkeys after subchronic phencyclidine exposure: involvement in frontostriatal cognitive deficits
Jentsch J, Taylor J, Elsworth J, Redmond D, Roth R. Altered frontal cortical dopaminergic transmission in monkeys after subchronic phencyclidine exposure: involvement in frontostriatal cognitive deficits. Neuroscience 1999, 90: 823-832. PMID: 10218783, DOI: 10.1016/s0306-4522(98)00481-3.Peer-Reviewed Original ResearchConceptsCognitive deficitsSubchronic phencyclidine administrationDorsolateral prefrontal cortexFrontal cortexCortical dopamine transmissionReduced dopaminergic functionFrontostriatal functionDetour taskCognitive performanceDopamine utilizationPhencyclidine exposurePrefrontal cortexPerformance impairmentPrelimbic cortexBrain regionsCognitive dysfunctionCortical impairmentCortical regionsCognitive impairmentDopaminergic functionPhencyclidine administrationDopamine transmissionSpecific subregionsCortexPsychotomimetic drug phencyclidineDopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys
Jentsch J, Taylor J, Redmond Jr D, Elsworth J, Youngren K, Roth R. Dopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys. Psychopharmacology 1999, 142: 78-84. PMID: 10102786, DOI: 10.1007/s002130050865.Peer-Reviewed Original ResearchConceptsFrontostriatal systemCognitive functionPrefrontal cortexObject retrieval taskRegulation of cognitionPrimate prefrontal cortexD4 dopamine receptorsNormal control monkeysDR antagonistsCognitive processesDetour taskCognitive deficitsPerformance impairmentBrain regionsCognitive dysfunctionRetrieval tasksFrontal cortexTaskCortexCortical dopaminergicDeficitsDopaminergic systemAntagonist reversalControl subjectsDopamine receptors
1998
Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion
Jentsch J, Taylor J, Roth R. Subchronic Phencyclidine Administration Increases Mesolimbic Dopaminergic System Responsivity and Augments Stress- and Psychostimulant-Induced Hyperlocomotion. Neuropsychopharmacology 1998, 19: 105-113. PMID: 9629564, DOI: 10.1016/s0893-133x(98)00004-9.Peer-Reviewed Original ResearchMeSH Keywords3,4-Dihydroxyphenylacetic AcidAnalysis of VarianceAnimalsBrainDextroamphetamineDisease Models, AnimalDizocilpine MaleateDopamineDrug Administration ScheduleHaloperidolLimbic SystemMaleMotor ActivityPhencyclidinePrefrontal CortexRatsRats, Sprague-DawleySchizophreniaStress, PsychologicalTime FactorsConceptsDopamine utilizationHaloperidol-induced increasePCP exposureFrontal cortical dysfunctionAmphetamine-induced hyperlocomotionSubchronic PCP administrationMesolimbic dopamine transmissionPCP-treated ratsCortical dopaminergicCortical dysfunctionDopaminergic deficitDopaminergic transmissionDopaminergic functionDopamine transmissionDopaminergic hypoactivityPCP administrationBehavioral pathologyCognitive deficitsRatsSystem responsivityHyperlocomotionDopaminergicExposureCurrent studyDeficitsPrefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence
Jentsch J, Tran A, Taylor J, Roth R. Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neurochemical evidence. Psychopharmacology 1998, 138: 89-95. PMID: 9694531, DOI: 10.1007/s002130050649.Peer-Reviewed Original ResearchConceptsMesolimbic dopamine systemPrefrontal cortexInduced hyperlocomotionDopamine neuronsDopamine releaseNucleus accumbensDopamine systemInjection of phencyclidineMesocorticolimbic dopaminergic neuronsMesolimbic dopamine neuronsVentral tegmental areaCell body regionIbotenic acid lesionsPrefrontal Cortical InvolvementProfound cognitive impairmentGlutamatergic releaseNeurochemical evidenceAcute administrationCortical involvementDopamine utilizationDopaminergic neuronsMesolimbic pathwayTegmental areaAcid lesionsDopaminergic activationIn vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector
During M, Samulski R, Elsworth J, Kaplitt M, Leone P, Xiao X, Li J, Freese A, Taylor J, Roth R, Sladek J, O’Malley K, Redmond D. In vivo expression of therapeutic human genes for dopamine production in the caudates of MPTP-treated monkeys using an AAV vector. Gene Therapy 1998, 5: 820-827. PMID: 9747462, DOI: 10.1038/sj.gt.3300650.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsAromatic-L-Amino-Acid DecarboxylasesChlorocebus aethiopsDependovirusDopamineDopamine AgentsGene ExpressionGene Transfer TechniquesGenetic VectorsHumansImmunohistochemistryMaleParkinson DiseaseTrigeminal Caudal NucleusTyrosine 3-MonooxygenaseConceptsTyrosine hydroxylaseStriatal cellsDopamine-depleted monkeysAdeno-associated virus vectorProduction of dopamineParkinsonian monkeysTransient feverSevere hyperactivityStriatal dopaminePrimate neuronsStereotactic injectionHistological evidencePrimate modelInjection tractNeurotoxin MPTPDopamine productionParkinson's diseaseTreatment groupsSignificant toxicityBehavioral effectsVivo gene therapyElevated levelsBiochemical effectsFirst dayMonkeysIntrastriatal Grafts From Multiple Donors Do Not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates
Sladek J, Collier T, Elsworth J, Roth R, Taylor J, Redmond D. Intrastriatal Grafts From Multiple Donors Do Not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates. Cell Transplantation 1998, 7: 87-96. DOI: 10.1016/s0963-6897(98)00007-4.Peer-Reviewed Original ResearchConceptsDopamine neuronsDouble graftsAdult African green monkeysVentral mesencephalic dopamine neuronsMultiple donorsGrafts of tissueMore dopamine neuronsSymptoms of parkinsonismMesencephalic dopamine neuronsDopamine cell survivalHuman clinical trialsAfrican green monkeysIntrastriatal graftsPositive neuronsTotal numberClinical trialsDopamine levelsCaudate nucleusRecipient animalsGraftGrafted tissueNeuronsGreen monkeysNonhuman primatesDorsoventral extentIntrastriatal Grafts from Multiple Donors do not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates
Sladek J, Collier T, Elsworth J, Roth R, Taylor J, Redmond D. Intrastriatal Grafts from Multiple Donors do not Result in a Proportional Increase in Survival of Dopamine Neurons in Nonhuman Primates. Cell Transplantation 1998, 7: 87-96. PMID: 9588591, DOI: 10.1177/096368979800700204.Peer-Reviewed Original ResearchConceptsDopamine neuronsDouble graftsAdult African green monkeysVentral mesencephalic dopamine neuronsMultiple donorsGrafts of tissueMore dopamine neuronsSymptoms of parkinsonismMesencephalic dopamine neuronsDopamine cell survivalHuman clinical trialsAfrican green monkeysIntrastriatal graftsPositive neuronsTotal numberClinical trialsDopamine levelsCaudate nucleusRecipient animalsGraftGrafted tissueNeuronsGreen monkeysNonhuman primatesDorsoventral extent
1997
(S)-(-)-HA-966, a gamma-hydroxybutyrate-like agent, prevents enhanced mesocorticolimbic dopamine metabolism and behavioral correlates of restraint stress, conditioned fear and cocaine sensitization.
Morrow B, Lee E, Taylor J, Elsworth J, Nye H, Roth R. (S)-(-)-HA-966, a gamma-hydroxybutyrate-like agent, prevents enhanced mesocorticolimbic dopamine metabolism and behavioral correlates of restraint stress, conditioned fear and cocaine sensitization. Journal Of Pharmacology And Experimental Therapeutics 1997, 283: 712-21. PMID: 9353390.Peer-Reviewed Original ResearchConceptsHA-966Dopamine metabolismMedial prefrontal cortexCocaine sensitizationNucleus accumbensHigh doseAcute cocaine-induced locomotionPrefrontal cortexGABAB receptor bindingCocaine-induced locomotionGamma-aminobutyric acidStress-induced increaseFear-inducing behaviorDopamine utilizationGABAB receptorsRestraint stressControl ratsLocomotor sensitizationDopaminergic neurotransmissionShell subdivisionBaclofen bindingCortical membranesPositive enantiomerWeight gainReceptor bindingSupranormal Stimulation of D1 Dopamine Receptors in the Rodent Prefrontal Cortex Impairs Spatial Working Memory Performance
Zahrt J, Taylor J, Mathew R, Arnsten A. Supranormal Stimulation of D1 Dopamine Receptors in the Rodent Prefrontal Cortex Impairs Spatial Working Memory Performance. Journal Of Neuroscience 1997, 17: 8528-8535. PMID: 9334425, PMCID: PMC6573725, DOI: 10.1523/jneurosci.17-21-08528.1997.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzazepinesDopamineDopamine AgonistsDopamine AntagonistsInfusions, ParenteralMaleMaze LearningMemoryModels, NeurologicalModels, PsychologicalPrefrontal CortexPsychomotor PerformanceRatsRats, Sprague-DawleyReceptors, Dopamine D1Receptors, N-Methyl-D-AspartateSpatial BehaviorStress, PsychologicalConceptsD1 receptor stimulationPrefrontal cortexReceptor stimulationSKF 81297SCH 23390D1 receptorsSupranormal stimulationPFC of ratsD1 receptor mechanismsDA receptor stimulationDose-related impairmentD1 receptor antagonistD1 receptor agonistD1 dopamine receptorsDelayed-alternation performanceMemory functionRecent electrophysiological studiesSpatial Working Memory PerformanceReceptor antagonistReceptor agonistDopamine receptorsReceptor mechanismsElectrophysiological studiesHigh dosesDrug efficacyEnduring Cognitive Deficits and Cortical Dopamine Dysfunction in Monkeys After Long-Term Administration of Phencyclidine
Jentsch J, Redmond D, Elsworth J, Taylor J, Youngren K, Roth R. Enduring Cognitive Deficits and Cortical Dopamine Dysfunction in Monkeys After Long-Term Administration of Phencyclidine. Science 1997, 277: 953-955. PMID: 9252326, DOI: 10.1126/science.277.5328.953.Peer-Reviewed Original ResearchConceptsDopamine utilizationPrefrontal cortexAtypical antipsychotic drug clozapineLong-term administrationDirect drug effectAntipsychotic drug clozapinePsychotomimetic drug phencyclidineAdministration of phencyclidineDorsolateral prefrontal cortexDopamine hypofunctionPrefrontal cortex functionCognitive dysfunctionPhencyclidine treatmentBehavioral deficitsDopamine dysfunctionPsychiatric disordersDrug effectsDrug clozapineDrug phencyclidineBrain regionsCognitive deficitsCortex functionCognitive functionPhencyclidineCortexMetabolic energy capacity of dopaminergic grafts and the implanted striatum in parkinsonian nonhuman primates as visualized with cytochrome oxidase histochemistry
Collier T, Redmond D, Roth R, Elsworth J, Taylor J, Sladek J. Metabolic energy capacity of dopaminergic grafts and the implanted striatum in parkinsonian nonhuman primates as visualized with cytochrome oxidase histochemistry. Cell Transplantation 1997, 6: 135-140. DOI: 10.1016/s0963-6897(97)00003-1.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsBrain Tissue TransplantationChlorocebus aethiopsCorpus StriatumDopamineElectron Transport Complex IVEnergy MetabolismFetal Tissue TransplantationGestational AgeImmunohistochemistryMesencephalonNeuronsParkinson Disease, SecondaryTyrosine 3-MonooxygenaseConceptsDA neuronsEmbryonic ventral mesencephalic tissueParkinsonian nonhuman primatesStriatum of DATyrosine hydroxylase immunocytochemistryVentral mesencephalic tissueVentral mesencephalic graftsCytochrome oxidase histochemistryCytochrome oxidase stainingMitochondrial enzyme cytochrome oxidaseLocal energy metabolismActive innervationBilateral graftsNeuron contentDopaminergic graftsMesencephalic graftsMesencephalic tissueHost brainBrain metabolismEnzyme cytochrome oxidaseCO stainingTissue transplantsGraftMetabolic activityNonhuman primatesMetabolic Energy Capacity of Dopaminergic Grafts and the Implanted Striatum in Parkinsonian Nonhuman Primates as Visualized with Cytochrome Oxidase Histochemistry
Collier T, Redmond D, Roth R, Elsworth J, Taylor J, Sladek J. Metabolic Energy Capacity of Dopaminergic Grafts and the Implanted Striatum in Parkinsonian Nonhuman Primates as Visualized with Cytochrome Oxidase Histochemistry. Cell Transplantation 1997, 6: 135-140. PMID: 9142445, DOI: 10.1177/096368979700600207.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAnimalsBrain Tissue TransplantationChlorocebus aethiopsCorpus StriatumDopamineElectron Transport Complex IVEnergy MetabolismFetal Tissue TransplantationGestational AgeImmunohistochemistryMesencephalonNeuronsParkinson Disease, SecondaryTyrosine 3-MonooxygenaseConceptsDA neuronsEmbryonic ventral mesencephalic tissueParkinsonian nonhuman primatesStriatum of DATyrosine hydroxylase immunocytochemistryVentral mesencephalic tissueVentral mesencephalic graftsBrain energy metabolismCytochrome oxidase histochemistryCytochrome oxidase stainingMitochondrial enzyme cytochrome oxidaseLocal energy metabolismEnergy metabolismActive innervationBilateral graftsNeuron contentDopaminergic graftsMesencephalic graftsMesencephalic tissueHost brainEnzyme cytochrome oxidaseCO stainingTissue transplantsGraftMetabolic activityDysregulation of Mesoprefrontal Dopamine Neurons Induced by Acute and Repeated Phencyclidine Administration in the Nonhuman Primate: Implications for Schizophrenia
Jentsch J, Elsworth J, Taylor J, Redmond D, Roth R. Dysregulation of Mesoprefrontal Dopamine Neurons Induced by Acute and Repeated Phencyclidine Administration in the Nonhuman Primate: Implications for Schizophrenia. Advances In Pharmacology 1997, 42: 810-814. PMID: 9328021, DOI: 10.1016/s1054-3589(08)60870-4.Peer-Reviewed Original ResearchConceptsPCP administrationAcute PCP administrationNegative symptomsDA systemMesoprefrontal dopamine neuronsSubcortical DA systemsBrains of patientsSchizophrenia-like symptomatologyDevelopment of neuropathologyDistinct behavioral effectsDAergic dysfunctionDA metabolismDAergic functionDopamine neuronsCognitive dysfunctionNovel agentsDeficits of schizophreniaFrontal cortexPsychotomimetic propertiesNeurobiological effectsDopamine systemPositive symptomsPhencyclidine administrationBehavioral effectsAdministration
1996
Early gestational mesencephalon grafts, but not later gestational mesencephalon, cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated monkeys
Elsworth J, Sladek J, Taylor J, Collier T, Redmond D, Roth R. Early gestational mesencephalon grafts, but not later gestational mesencephalon, cerebellum or sham grafts, increase dopamine in caudate nucleus of MPTP-treated monkeys. Neuroscience 1996, 72: 477-484. PMID: 8737417, DOI: 10.1016/0306-4522(95)00564-1.Peer-Reviewed Original ResearchConceptsFetal ventral mesencephalonVentral mesencephalonCaudate nucleusGraft siteDopamine neuronsDopamine concentrationsBehavioral recoveryTyrosine hydroxylase-positive neuronsHomovanillic acid/dopamine ratioFetal dopamine neuronsGrafted dopamine neuronsIntrastriatal transplantsParkinsonian primatesGrafted neuronsIntrastriatal transplantationGestational ageTransplant proceduresDopamine ratioDopamine productionSignificant elevationNucleus accumbensDopamine systemSham graftsGraftBrain regions