2001
Prenatal cocaine exposure increases mesoprefrontal dopamine neuron responsivity to mild stress
Elsworth J, Morrow B, Roth R. Prenatal cocaine exposure increases mesoprefrontal dopamine neuron responsivity to mild stress. Synapse 2001, 42: 80-83. PMID: 11574943, DOI: 10.1002/syn.1102.Peer-Reviewed Original ResearchConceptsPrenatal cocaine exposurePrefrontal cortexCocaine exposureShort-term memory deficitsVentromedial prefrontal cortexShort-term memoryMedial prefrontal cortexDopamine neuronsAdolescent ratsCognitive deficitsMemory deficitsMesoprefrontal dopamine systemPrenatal cocaineMild footshock stressDopamine systemDeficitsFootshock stressNeurobehavioral deficitsDopamine turnoverIntravenous modelRodent modelsBehavioral abnormalitiesFetal developmentMild stressCortexPrenatal exposure to cocaine reduces the number and enhances reactivity of A10 dopaminergic neurons to environmental stress
Morrow B, Elsworth J, Roth R. Prenatal exposure to cocaine reduces the number and enhances reactivity of A10 dopaminergic neurons to environmental stress. Synapse 2001, 41: 337-344. PMID: 11494404, DOI: 10.1002/syn.1090.Peer-Reviewed Original ResearchConceptsA10 dopamine neuronsDopamine neuronsDopaminergic neuronsPrenatal exposurePrenatal saline controlsTyrosine hydroxylase immunoreactiveA10 dopaminergic neuronsCocaine-induced reductionRat dopaminergic neuronsCocaine-exposed ratsPoor cognitive performanceYoung adult offspringUnderlying biochemical changesDopaminergic functionA9 regionSaline controlsIntravenous modelPerinatal lossAdult offspringIntermittent footshockImmediate early genesCognitive deficitsNeuronal systemsBehavioral effectsCell groupsGlial Cell Line-Derived Neurotrophic Factor (GDNF) Gene Delivery Protects Dopaminergic Terminals from Degeneration
Connor B, Kozlowski D, Unnerstall J, Elsworth J, Tillerson J, Schallert T, Bohn M. Glial Cell Line-Derived Neurotrophic Factor (GDNF) Gene Delivery Protects Dopaminergic Terminals from Degeneration. Experimental Neurology 2001, 169: 83-95. PMID: 11312561, DOI: 10.1006/exnr.2001.7638.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAutoradiographyCarrier ProteinsCocaineCorpus StriatumDisease Models, AnimalDopamineDopamine Plasma Membrane Transport ProteinsGenetic TherapyGenetic VectorsGlial Cell Line-Derived Neurotrophic FactorMaleMembrane GlycoproteinsMembrane Transport ProteinsMicroinjectionsMotor ActivityNerve Growth FactorsNerve Tissue ProteinsNeuronsNeurotransmitter AgentsOxidopamineParkinson Disease, SecondaryPresynaptic TerminalsRatsRats, Inbred F344RNA, MessengerSubstantia NigraTyrosine 3-MonooxygenaseConceptsGlial cell line-derived neurotrophic factorGDNF gene deliverySubstantia nigraDA terminalsDA neuronsNeuronal sproutingGlial cell line-derived neurotrophic factor (GDNF) gene deliveryAmphetamine-induced rotational asymmetryLine-derived neurotrophic factorUnilateral intrastriatal injectionAged rat brainDopaminergic neuronal functionTyrosine hydroxylase mRNADA transporter ligandsNigrostriatal functionStriatal injectionAxonal sproutingDopaminergic terminalsIntrastriatal injectionStriatal denervationDenervated striatumWeeks postlesionNeurotrophic factorNigrostriatal axonsPartial lesionsNicotine Receptor Inactivation Decreases Sensitivity to Cocaine
Zachariou V, Caldarone B, Weathers-Lowin A, George T, Elsworth J, Roth R, Changeux J, Picciotto M. Nicotine Receptor Inactivation Decreases Sensitivity to Cocaine. Neuropsychopharmacology 2001, 24: 576-589. PMID: 11282258, DOI: 10.1016/s0893-133x(00)00224-4.Peer-Reviewed Original ResearchConceptsPlace preferenceDA turnoverLow doseHigh-affinity nicotinic acetylcholine receptorsMesolimbic DA systemHigh-affinity nAChRsNicotinic antagonist mecamylamineWild-type miceMesolimbic dopamine systemFos-related antigensProperties of nicotineCocaine place preferenceΒ2 subunitNicotinic acetylcholine receptorsAntagonist mecamylamineDA releaseMetabolite DOPACNeurochemical changesSubthreshold doseType miceDopamine systemPsychomotor stimulantsAcetylcholine receptorsHigh dosesBrain regions
2000
Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson's Disease and Memory
Leranth C, Roth R, Elsworth J, Naftolin F, Horvath T, Redmond D. Estrogen Is Essential for Maintaining Nigrostriatal Dopamine Neurons in Primates: Implications for Parkinson's Disease and Memory. Journal Of Neuroscience 2000, 20: 8604-8609. PMID: 11102464, PMCID: PMC6773080, DOI: 10.1523/jneurosci.20-23-08604.2000.Peer-Reviewed Original ResearchConceptsNigrostriatal dopamine neuronsDopamine neuronsParkinson's diseaseSubstantia nigraDopamine cellsTyrosine hydroxylase-expressing neuronsTyrosine hydroxylase-immunoreactive cellsNigral dopamine systemsEstrogen replacement therapyNew treatment strategiesUnbiased stereological analysisTypes of neuronsProgression of diseaseEstrogen replacementPostmenopausal womenEstrogen deprivationReplacement therapyTreatment strategiesCompact zoneGonadal hormonesLong-term effectsDopamine systemEstrogenDiseaseNeuronsTMT, a predator odor, elevates mesoprefrontal dopamine metabolic activity and disrupts short-term working memory in the rat
Morrow B, Roth R, Elsworth J. TMT, a predator odor, elevates mesoprefrontal dopamine metabolic activity and disrupts short-term working memory in the rat. Brain Research Bulletin 2000, 52: 519-523. PMID: 10974491, DOI: 10.1016/s0361-9230(00)00290-2.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexPrefrontal cortexExploratory behaviorSample taskFamiliar objectsNovel objectsMesoprefrontal dopamine neuronsTrimethylthiazolineMemoryPsychological stressTMT exposureObject recognition methodPredator odorSet of objectsCortexElevated serum corticosteroneDopaminergic inputDopaminergic activityBrief exposureDopaminergic innervationSerum corticosteroneDopamine neuronsDopamine metabolismObjectsRecognition methodThe predator odor, TMT, displays a unique, stress-like pattern of dopaminergic and endocrinological activation in the rat
Morrow B, Redmond A, Roth R, Elsworth J. The predator odor, TMT, displays a unique, stress-like pattern of dopaminergic and endocrinological activation in the rat. Brain Research 2000, 864: 146-151. PMID: 10793199, DOI: 10.1016/s0006-8993(00)02174-0.Peer-Reviewed Original ResearchConceptsDopamine metabolismSerum corticosteroneAcute exposureCentral dopamine metabolismNucleus accumbens coreMedial prefrontal cortexFear-inducing behaviorPredator odorCentral effectsAccumbens coreRatsStressful stimuliPrefrontal cortexConditioned fearAltered behaviorControl odorAversive stimuliCorticosteroneMetabolismOpen fieldBiochemical activationUnique patternExposureActivationTMTDivergent effects of putative anxiolytics on stress‐induced Fos expression in the mesoprefrontal system of the rat
Morrow B, Elsworth J, Lee E, Roth R. Divergent effects of putative anxiolytics on stress‐induced Fos expression in the mesoprefrontal system of the rat. Synapse 2000, 36: 143-154. PMID: 10767061, DOI: 10.1002/(sici)1098-2396(200005)36:2<143::aid-syn7>3.0.co;2-h.Peer-Reviewed Original ResearchConceptsVentral tegmental areaFos-LITegmental areaMedial prefrontal cortexPutative anxiolyticsBenzodiazepine agonistsStress-induced Fos-like immunoreactivityPartial agonistStress-induced Fos expressionGlycine/NMDA receptorPrefrontal cortexMesoprefrontal dopamine neuronsPutative anxiolytic agentsTH-LI cellsSaline-treated ratsFos-like immunoreactivityAnxiolytic-like actionFos-LI nucleiWeak partial agonistStress-induced increaseFear-inducing behaviorFootshock paradigmAlpha2 agonistsStress-induced activationDopaminergic neurons
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) modelSpontaneous 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 regionThe role of mesoprefrontal dopamine neurons in the acquisition and expression of conditioned fear in the rat
Morrow B, Elsworth J, Rasmusson A, Roth R. The role of mesoprefrontal dopamine neurons in the acquisition and expression of conditioned fear in the rat. Neuroscience 1999, 92: 553-564. PMID: 10408604, DOI: 10.1016/s0306-4522(99)00014-7.Peer-Reviewed Original ResearchConceptsFear conditioningMesoprefrontal dopamine neuronsClassical fear conditioningMedial prefrontal cortexDopamine neuronsFear responsesConditioned fearPrefrontal cortexFearful behaviorNormal extinctionConditioned responsePsychological stressorsRate of extinctionStress-related changesSham-lesioned ratsConditioningFearAcquisition periodDopamine metabolismNucleus accumbensDopamine levelsAcquisitionRatsNeuronsLesionsAltered 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 phencyclidineBiochemical and behavioral anxiolytic-like effects of R(+)HA-966 at the level of the ventral tegmental area in rats
Morrow B, Elsworth J, Zito C, Roth R. Biochemical and behavioral anxiolytic-like effects of R(+)HA-966 at the level of the ventral tegmental area in rats. Psychopharmacology 1999, 143: 227-234. PMID: 10353424, DOI: 10.1007/s002130050941.Peer-Reviewed Original ResearchConceptsVentral tegmental areaHA-966Expression sessionsIntra-VTADopamine metabolismTegmental areaGlycine/NMDA receptor complexPrefrontal cortexMesoprefrontal dopamine neuronsAnxiolytic-like effectsAnxiolytic-like actionDopamine cell bodiesNMDA receptor complexWeak partial agonistMedial prefrontal cortexStress-induced activationCannula implantationDopamine neuronsControl ratsLocal injectionPartial agonistRatsCell bodiesPsychological stressorsStress-induced changesDopamine 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
In 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 bindingEnduring 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 primates