2007
α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex
Wang M, Ramos BP, Paspalas CD, Shu Y, Simen A, Duque A, Vijayraghavan S, Brennan A, Dudley A, Nou E, Mazer JA, McCormick DA, Arnsten AF. α2A-Adrenoceptors Strengthen Working Memory Networks by Inhibiting cAMP-HCN Channel Signaling in Prefrontal Cortex. Cell 2007, 129: 397-410. PMID: 17448997, DOI: 10.1016/j.cell.2007.03.015.Peer-Reviewed Original ResearchConceptsHCN channel blockadePrefrontal cortical neuronsDelay-related firingΑ2A adrenoceptorsChannel blockadeCortical neuronsInhibition of cAMPAlpha2A adrenoceptorsDendritic spinesNetwork firingElectrophysiological studiesPFC neuronsRecurrent excitationFunctional connectivityHCN channelsPrefrontal cortexHCN1 channelsPFC networksCAMP inhibitionStimulationBlockade
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 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 performanceGenetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function
ARNSTEN A, Lombroso P. Genetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function. Journal Of The American Academy Of Child & Adolescent Psychiatry 2000, 39: 1201-1203. PMID: 10986819, DOI: 10.1097/00004583-200009000-00022.Peer-Reviewed Original Research
1999
Treatment 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 monkeysMonkeysLocal infusion of an α-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys
Mao Z, Arnsten A, Li B. Local infusion of an α-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys. Biological Psychiatry 1999, 46: 1259-1265. PMID: 10560031, DOI: 10.1016/s0006-3223(99)00139-0.Peer-Reviewed Original ResearchConceptsAlpha-2 adrenoceptorsRat prefrontal cortexPrefrontal cortexAlpha-1 adrenoceptor stimulationAlpha-1 adrenergic agonist phenylephrineAlpha-1 adrenoceptorsAdrenergic agonist phenylephrineDorsolateral prefrontal cortexAgonist phenylephrinePhenylephrine infusionAdrenoceptor stimulationLocal infusionAgonist guanfacineAdrenergic agonistsPrefrontal cortex impairsAdrenoceptorsDelayed-response taskInfusionAlpha 1Rat experimentsStimulationMonkeysGuanfacineSWM functionSWM performanceRole 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 ResearchMeSH KeywordsAdrenergic alpha-AgonistsAntidepressive Agents, TricyclicArousalCatecholaminesHumansMemoryMonoamine Oxidase InhibitorsNorepinephrineStress Disorders, Post-TraumaticConceptsRole 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 stressα-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function
Arnsten A, Mathew R, Ubriani R, Taylor J, Li B. α-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function. Biological Psychiatry 1999, 45: 26-31. PMID: 9894572, DOI: 10.1016/s0006-3223(98)00296-0.Peer-Reviewed Original ResearchConceptsPrefrontal cortexCognitive functionPrefrontal cortical cognitive functionCortical cognitive functionsImpairs cognitive functionHigher cortical functionsMemory taskAlpha-1 adrenoceptorsMost antipsychotic medicationsAlternation performanceNoradrenergic turnoverCortical functionPhenylephrine responseAlpha-1 adrenoceptor stimulationNeuropsychiatric disordersAlpha-1 adrenergic antagonistAlpha-1 adrenergic agonistDisordersAntipsychotic medicationAnxietyHigh levelsPhenylephrine infusionAdrenoceptor stimulationAdrenergic antagonistsSecond messenger pathways
1998
The 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
The Alpha-1 Adrenergic Agonist, Cirazoline, Impairs Spatial Working Memory Performance in Aged Monkeys
Arnsten A, Jentsch JD. The Alpha-1 Adrenergic Agonist, Cirazoline, Impairs Spatial Working Memory Performance in Aged Monkeys. Pharmacology Biochemistry And Behavior 1997, 58: 55-59. PMID: 9264070, DOI: 10.1016/s0091-3057(96)00477-7.Peer-Reviewed Original ResearchConceptsAlpha-1 adrenergic agonistAdrenergic antagonistsAdrenergic agonistsAlpha-1 adrenergic antagonistAlpha-1 adrenergic receptorsAdditional high affinityGood brain penetranceAlpha 2 receptorsAdrenergic receptor stimulationPrefrontal cortical functionSpatial Working Memory PerformanceBrain penetranceImidazoline receptorsCortical functionNonspecific changesCirazolineControl trialMemory performanceReceptor stimulationAdrenergic receptorsLow dosesRhesus monkeysAged monkeysPrefrontal cortexDrug actionNoradrenergic 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
1993
Catecholamine mechanisms in age-related cognitive decline
Arnsten A. Catecholamine mechanisms in age-related cognitive decline. Neurobiology Of Aging 1993, 14: 639-641. PMID: 7905190, DOI: 10.1016/0197-4580(93)90054-f.Peer-Reviewed Original ResearchAdrenergic alpha-AgonistsAgingAnimalsCatecholaminesCognitionHaplorhiniHumansReceptors, Adrenergic, alpha-2
1991
Behavioral and receptor binding analysis of the α2-adrenergic agonist, 5-bromo-6 [2-imidazoline-2-YL amino] quinoxaline (UK-14304): evidence for cognitive enhancement at an α2-adrenoceptor subtype
Arnsten A, Leslie FM. Behavioral and receptor binding analysis of the α2-adrenergic agonist, 5-bromo-6 [2-imidazoline-2-YL amino] quinoxaline (UK-14304): evidence for cognitive enhancement at an α2-adrenoceptor subtype. Neuropharmacology 1991, 30: 1279-1289. PMID: 1686301, DOI: 10.1016/0028-3908(91)90024-6.Peer-Reviewed Original Research
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