2024
The meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition
Magrou L, Joyce M, Froudist-Walsh S, Datta D, Wang X, Martinez-Trujillo J, Arnsten A. The meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition. Cerebral Cortex 2024, 34: bhae174. PMID: 38771244, PMCID: PMC11107384, DOI: 10.1093/cercor/bhae174.Peer-Reviewed Original ResearchConceptsInter-areal connectionsVisual cortexPrimary visual cortexHigher cortical areasMacaque cortexPrimate specializationHigher cognitionPrimate cortexV1Working memory storageDendritic spine densityTop-down regulationPrefrontal cortexConnection structureSpine densityFunctional segregationCortical areasFrontal areasCortexConnectomeNetwork organizationMemory storageMultimodal association
2014
A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation
McKee SA, Potenza MN, Kober H, Sofuoglu M, Arnsten A, Picciotto MR, Weinberger AH, Ashare R, Sinha R. A translational investigation targeting stress-reactivity and prefrontal cognitive control with guanfacine for smoking cessation. Journal Of Psychopharmacology 2014, 29: 300-311. PMID: 25516371, PMCID: PMC4376109, DOI: 10.1177/0269881114562091.Peer-Reviewed Original ResearchConceptsPlacebo-treated subjectsFunctional magnetic resonance imagingCentral noradrenergic pathwaysPrefrontal cognitive dysfunctionSystolic blood pressureClinical outcome dataAd libitum smokingNovel translational approachStress-induced reinstatementMagnetic resonance imagingNicotine-deprived smokersBlood pressureNoradrenergic pathwaysAgonist guanfacineCognitive dysfunctionTreatment periodTobacco cravingQuit attemptsOutcome dataSmokingComplete abstinenceCortisol levelsTranslational investigationsCigarette useGuanfacine
2013
Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 12078-12083. PMID: 23818597, PMCID: PMC3718126, DOI: 10.1073/pnas.1307849110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnalysis of VarianceAnimalsBridged Bicyclo Compounds, HeterocyclicCholinergic AgonistsCholinergic AntagonistsCognitionFemaleIontophoresisMacaca mulattaMaleMecamylamineMicroscopy, ImmunoelectronN-MethylaspartatePhenolsPiperidinesPrefrontal CortexQuinuclidinesReceptors, NicotinicSpatial BehaviorSynapsesVisual PerceptionConceptsDorsolateral prefrontal cortexΑ7 nAChRsPrefrontal cortexΑ7 nicotinic acetylcholine receptorGlutamatergic NMDA receptorsCognitive circuitsNicotinic α7 receptorsPrimary visual cortexNMDA receptor actionGenetic insultsNicotinic acetylcholine receptorsDlPFC circuitsPrimate dlPFCACh depletionNMDA actionNMDA receptorsPyramidal cellsΑ7 receptorsNeuronal firingNAChR blockadeAcetylcholine receptorsVisual cortexPersistent firingCognitive functionLow-dose stimulation
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
The 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 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
A role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in the prefrontal cortex
Birnbaum S, Gobeske K, Auerbach J, Taylor J, Arnsten A. A role for norepinephrine in stress-induced cognitive deficits: α-1-adrenoceptor mediation in the prefrontal cortex. Biological Psychiatry 1999, 46: 1266-1274. PMID: 10560032, DOI: 10.1016/s0006-3223(99)00138-9.Peer-Reviewed Original ResearchConceptsStress-induced cognitive deficitsPoor attention regulationAlternation performanceSpatial working memoryPFC cognitive functionPrefrontal cortical dysfunctionMotor response timeIntra-PFC infusionsStress-induced deficitsStress-induced impairmentWorking memoryAttention regulationPFC contributeMemory performanceAlternation testingStress researchNeuropsychiatric disordersPrefrontal cortexCognitive deficitsCognitive functionMemory functionMemory impairmentPFC dysfunctionPerseverative patternsPharmacological stressorTreatment 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 monkeysMonkeysα-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
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 actionThe effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys
Arnsten A, Lin C, Van Dyck C, Stanhope K. The effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys. Neurobiology Of Aging 1997, 18: 21-28. PMID: 8983029, DOI: 10.1016/s0197-4580(96)00162-5.Peer-Reviewed Original ResearchConceptsVisual object discriminationObject discriminationFine motor tasksMotor tasksCognitive-enhancing effectsMemory taskResponse taskCognitive performanceReceptor antagonistEnhanced acquisitionCognitive functionReliable improvementMarmoset researchAged monkeysTaskReversal conditionsWide dose rangeDiscriminationSide effectsLow dosesRhesus monkeysDose rangeAntagonistAcquisitionMonkeysNoradrenergic 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
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 monkeysMonkeysCatecholamine 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 Research
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
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