2002
Actions of α-2 noradrenergic agonists on spatial working memory and blood pressure in rhesus monkeys appear to be mediated by the same receptor subtype
Franowicz JS, Arnsten A. Actions of α-2 noradrenergic agonists on spatial working memory and blood pressure in rhesus monkeys appear to be mediated by the same receptor subtype. Psychopharmacology 2002, 162: 304-312. PMID: 12122489, DOI: 10.1007/s00213-002-1110-6.Peer-Reviewed Original ResearchConceptsSame receptor subtypeReceptor subtypesBlood pressureCognitive improvementHypotensive effectNoradrenergic agonistsRhesus monkeysDose-dependent reversalCognitive-enhancing effectsNon-human primatesIdazoxan doseCognitive enhancementMK-912Same dosesHypotensionLow dosesAgonistsSubtypesPotent antagonistAntagonistMK912Recent evidenceClonidineIdazoxanDoses
2000
Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats
Birnbaum SG, Podell DM, Arnsten A. Noradrenergic alpha-2 receptor agonists reverse working memory deficits induced by the anxiogenic drug, FG7142, in rats. Pharmacology Biochemistry And Behavior 2000, 67: 397-403. PMID: 11164065, DOI: 10.1016/s0091-3057(00)00306-3.Peer-Reviewed Original ResearchConceptsReceptor agonistMemory deficitsAnxiogenic drugsSide effectsAlpha-1 receptor stimulationAlpha-2 adrenoceptor subtypesAlpha-2 receptor agonistCognitive deficitsPrefrontal cortexStress-related neuropsychiatric disordersImidazoline I1 receptor agonistHypotensive side effectsEfficacy of clonidineI1 receptor agonistPrefrontal cognitive deficitsPrefrontal cortical functionClonidine pretreatmentDA turnoverAdrenoceptor agonistsAdrenoceptor subtypesCatecholamine releaseReceptor subtypesCortical functionTherapeutic usefulnessReceptor stimulationThe Selective Dopamine D4 Receptor Antagonist, PNU-101387G, Prevents Stress-Induced Cognitive Deficits in Monkeys
Arnsten A, Murphy B, Merchant K. The Selective Dopamine D4 Receptor Antagonist, PNU-101387G, Prevents Stress-Induced Cognitive Deficits in Monkeys. Neuropsychopharmacology 2000, 23: 405-410. PMID: 10989267, DOI: 10.1016/s0893-133x(00)00133-0.Peer-Reviewed Original ResearchConceptsD4 receptor antagonistReceptor mechanismsReceptor antagonistDopamine D1 receptor mechanismsStress-induced cognitive dysfunctionPrefrontal cortexSelective dopamine D4 receptor antagonistSelective D4 receptor antagonistD1 receptor mechanismsDose-related reversalDopamine D4 receptor antagonistCognitive dysfunctionPharmacological stressorHigh dosesLow dosesMemory deficitsCognitive deficitsStress exposureFurther studiesCognitive functioningAntagonistFG7142DosesPreliminary findingsMonkeysThe Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task
Avery R, Franowicz J, Studholme C, van Dyck C, Arnsten A. The Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task. Neuropsychopharmacology 2000, 23: 240-249. PMID: 10942848, DOI: 10.1016/s0893-133x(00)00111-1.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-2 Receptor AgonistsAdrenergic alpha-AgonistsAnimalsCerebrovascular CirculationCognitionFemaleGuanfacineImage Processing, Computer-AssistedMacaca mulattaMagnetic Resonance ImagingMemoryPrefrontal CortexSpace PerceptionStimulation, ChemicalTomography, Emission-Computed, Single-PhotonConceptsRegional cerebral blood flowCerebral blood flowPrefrontal cortexDorsolateral prefrontal cortexBlood flowAlpha 2A-adrenoceptorsAuditory association areasSuperior temporal cortexBlood flow tracerSPECT measuresAdrenoceptor agonistsAdrenoceptor stimulationAlpha-2aMemory taskAdrenoreceptor agonistIntravenous cathetersGuanfacine treatmentTemporal cortexRCBF valuesAssociation areasBrain regionsGuanfacineCortexSpatial Working Memory taskCognitive performanceThrough the Looking Glass: Differential Noradenergic Modulation of Prefrontal Cortical Function
Arnsten A. Through the Looking Glass: Differential Noradenergic Modulation of Prefrontal Cortical Function. Neural Plasticity 2000, 7: 133-146. PMID: 10709220, PMCID: PMC2565372, DOI: 10.1155/np.2000.133.Peer-Reviewed Original Research
1999
Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder
Southwick S, Bremner J, Rasmusson A, Morgan C, Arnsten A, Charney D. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biological Psychiatry 1999, 46: 1192-1204. PMID: 10560025, DOI: 10.1016/s0006-3223(99)00219-x.Peer-Reviewed Original ResearchConceptsRole of norepinephrineClinical studiesNorepinephrine's roleTrauma-related alterationsRe-experiencing symptomsFear-provoking stimuliTreatment of PTSDPosttraumatic stress disorderChronic uncontrollable stressPharmacologic treatmentClinical findingsNeuronal reactivityIntrusive memoriesAdrenergic blockersEnhanced encodingSelective attentionPreclinical studiesReceptor sensitivityAversive eventsNorepinephrineTraumatic stressNovel stimuliStress disorderMAO inhibitorsUncontrollable stressTreatment with the Noradrenergic Alpha-2 Agonist Clonidine, But Not Diazepam, Improves Spatial Working Memory in Normal Young Rhesus Monkeys
Franowicz J, Arnsten A. Treatment with the Noradrenergic Alpha-2 Agonist Clonidine, But Not Diazepam, Improves Spatial Working Memory in Normal Young Rhesus Monkeys. Neuropsychopharmacology 1999, 21: 611-621. PMID: 10516957, DOI: 10.1016/s0893-133x(99)00060-3.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-AgonistsAdrenergic alpha-AntagonistsAdrenergic Uptake InhibitorsAnimalsBehavior, AnimalClonidineCognitionDiazepamDose-Response Relationship, DrugFemaleHypnotics and SedativesIdazoxanMacaca mulattaMemoryReaction TimeReceptors, Adrenergic, alpha-2ReserpineSpace PerceptionConceptsAlpha 2 agonist clonidineEffects of clonidineSpatial working memoryChronic reserpine treatmentYoung adult monkeysPrefrontal cortical functionYoung adult humansYoung rhesus monkeysAgonist clonidineReserpine treatmentCortical functionClonidineHuman studiesAdult monkeysHigh dosesLow dosesRhesus monkeysAged monkeysNonhuman primatesDose rangeAdult humansInsufficient dosageConflicting resultsYoung monkeysMonkeys
1998
The biology of being frazzled.
Arnsten A. The biology of being frazzled. Science 1998, 280: 1711-2. PMID: 9660710, DOI: 10.1126/science.280.5370.1711.Peer-Reviewed Original ResearchThe α-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys
Franowicz JS, Arnsten A. The α-2a noradrenergic agonist, guanfacine, improves delayed response performance in young adult rhesus monkeys. Psychopharmacology 1998, 136: 8-14. PMID: 9537677, DOI: 10.1007/s002130050533.Peer-Reviewed Original ResearchConceptsYoung adult rhesus monkeysAdult rhesus monkeysHigh dosesDorsolateral prefrontal cortical functionRhesus monkeysDose of idazoxanEffects of guanfacinePrefrontal cortical functionAntagonist idazoxanNoradrenergic agonistsCatecholamine depletionMild sedationAdrenergic agonistsCortical functionDrug effectsAged animalsGuanfacineAdrenergic receptorsLow dosesAged monkeysEffective doseIntact animalsIdazoxanDosesYoung animals
1997
Supranormal 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 efficacyNoradrenergic Influences on Prefrontal Cortical Cognitive Function: Opposing Actions at Postjunctional α1 Versus α2-Adrenergic Receptors
Arnsten A, Steere JC, Jentsch DJ, Li BM. Noradrenergic Influences on Prefrontal Cortical Cognitive Function: Opposing Actions at Postjunctional α1 Versus α2-Adrenergic Receptors. Advances In Pharmacology 1997, 42: 764-767. PMID: 9328010, DOI: 10.1016/s1054-3589(08)60859-5.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPrefrontal cortexNE releaseΑ2 receptorsCognitive impairmentBeneficial effectsPFC functionBasal NE releasePrefrontal cortical cognitive functionΑ2-adrenergic receptorsCortical cognitive functionsPotential cognitive enhancersAttention deficit hyperactivity disorderMemory functionDeficit hyperactivity disorderPostsynaptic α1Α1d subtypesNE terminalsΑ-adrenoceptorsΑ2 agonistsLithium medicationNoradrenergic influenceOpen trialLithium pretreatmentΑ2A subtypeΑ2A receptors
1996
Dopamine and Spatial Working Memory in Rats and Monkeys: Pharmacological Reversal of Stress-Induced Impairment
Murphy B, Arnsten A, Jentsch J, Roth R. Dopamine and Spatial Working Memory in Rats and Monkeys: Pharmacological Reversal of Stress-Induced Impairment. Journal Of Neuroscience 1996, 16: 7768-7775. PMID: 8922432, PMCID: PMC6579090, DOI: 10.1523/jneurosci.16-23-07768.1996.Peer-Reviewed Original ResearchConceptsRodent prefrontal cortexPrefrontal cortexSpatial working memoryBenzodiazepine inverse agonist FG7142Stress-Induced ImpairmentsWorking memoryCognitive tasksVentral tegmental areaCognitive functioningCognitive deficitsMemory deficitsDopamine neuron cell bodiesD-cycloserineCognitive impairmentMultiple neurotransmitter systemsGlycine/NMDA antagonistsCognitionFG7142Dopamine turnoverTerminal field areasCurrent studyNeurotransmitter systemsDeficitsCortexImpairment
1995
Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys
Arnsten A, Cai J, Steere J, Goldman-Rakic P. Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys. Journal Of Neuroscience 1995, 15: 3429-3439. PMID: 7751922, PMCID: PMC6578230, DOI: 10.1523/jneurosci.15-05-03429.1995.Peer-Reviewed Original ResearchConceptsYoung adult monkeysFine motor tasksFine motor performanceAge-related cognitive declineAdult monkeysCognitive declineMotor performanceAged monkeysD2 dopamine receptor agonistDopamine D2 receptor mechanismsMotor tasksAged monkey brainsD2 receptor mechanismsDopamine receptor agonistsPrefrontal cortical cognitive functionEffects of quinpiroleD2 receptor functionCortical cognitive functionsAge-related lossDelayed response performanceQuinpirole responseDA depletionMotor cortexD2 autoreceptorsPostsynaptic receptors
1993
Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine
Arnsten A, Cai JX. Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine. Neurobiology Of Aging 1993, 14: 597-603. PMID: 7905189, DOI: 10.1016/0197-4580(93)90044-c.Peer-Reviewed Original ResearchConceptsPostsynaptic alpha-2 adrenoceptorsPostsynaptic alpha-2 receptorsAlpha-2 adrenoceptorsAlpha 2 receptorsAged monkeysAged animalsAlpha-2 receptor stimulationAlpha-2 adrenergic antagonistBeneficial effectsAlpha-2 antagonistAlpha-2 agonistsCognitive-enhancing effectsNE systemClonidine actsNE releaseAdrenergic antagonistsYohimbine treatmentReceptor stimulationLow dosesClonidineYohimbineNorepinephrineBeneficial dosesYoung monkeysMonkeys
1990
Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys
Arnsten A, Goldman-Rakic PS. Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys. Neurobiology Of Aging 1990, 11: 583-590. PMID: 1980719, DOI: 10.1016/0197-4580(90)90021-q.Peer-Reviewed Original Research
1988
The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes
Arnsten A, Cai J, Goldman-Rakic P. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. Journal Of Neuroscience 1988, 8: 4287-4298. PMID: 2903226, PMCID: PMC6569464, DOI: 10.1523/jneurosci.08-11-04287.1988.Peer-Reviewed Original ResearchConceptsAlpha-2 receptor subtypesB-HT920Alpha-2 agonistsReceptor subtypesRank order potencyLow dosesDose-response profilesBlood pressureSide effectsHigh dosesAlpha-2 adrenergic agonistsOrder potencyHypotensive side effectsSedative side effectsSubtypes of receptorsAged nonhuman primatesAged rhesus monkeysMemory-enhancing effectsMemory-impairing effectsClonidine effectAgonist guanfacineClonidineAdrenergic agonistsGuanfacineSedation
1985
α2-Adrenergic Mechanisms in Prefrontal Cortex Associated with Cognitive Decline in Aged Nonhuman Primates
Arnsten A, Goldman-Rakic P. α2-Adrenergic Mechanisms in Prefrontal Cortex Associated with Cognitive Decline in Aged Nonhuman Primates. Science 1985, 230: 1273-1276. PMID: 2999977, DOI: 10.1126/science.2999977.Peer-Reviewed Original ResearchConceptsBeneficial effectsAlpha-adrenergic systemReceptor agonist clonidineAlpha 2 receptorsΑ2-adrenergic mechanismsAged nonhuman primatesDorsolateral prefrontal cortexAgonist clonidineSite of actionAged humansPharmacological profileAged nonhumanCognitive declineCognitive deficitsCognitive functionPrefrontal cortexDrug actionNonhuman primatesMemory disordersClonidineLesionsCortex