2020
Muscarinic M1 Receptors Modulate Working Memory Performance and Activity via KCNQ Potassium Channels in the Primate Prefrontal Cortex
Galvin VC, Yang ST, Paspalas CD, Yang Y, Jin LE, Datta D, Morozov YM, Lightbourne TC, Lowet AS, Rakic P, Arnsten AFT, Wang M. Muscarinic M1 Receptors Modulate Working Memory Performance and Activity via KCNQ Potassium Channels in the Primate Prefrontal Cortex. Neuron 2020, 106: 649-661.e4. PMID: 32197063, PMCID: PMC7244366, DOI: 10.1016/j.neuron.2020.02.030.Peer-Reviewed Original ResearchConceptsKCNQ channelsInverted-U dose responseCell firingPrefrontal cortexMuscarinic M1 receptorsKCNQ potassium channelsSingle-unit recordingsPrimate prefrontal cortexDorsolateral prefrontal cortexCholinergic alterationsKCNQ isoformsM1 receptorsPyramidal neuronsCholinergic depletionMuscarinic M1Cognitive disordersAged monkeysPersistent firingRecurrent excitationPotassium channelsAppropriate targetsDose responseM1R stimulationSensory inputCortex
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 monkeysMonkeysAge-Related Cognitive Deficits and Neurotransmitters
Arnsten A. Age-Related Cognitive Deficits and Neurotransmitters. Cerebral Cortex 1999, 14: 89-110. DOI: 10.1007/978-1-4615-4885-0_5.Peer-Reviewed Original ResearchAge-related changesCognitive deficitsAge-related cognitive declineAge-related cognitive deficitsAged monkeysHigher cortical functionsSimilar neuropathological changesCognitive declineCortical functionDeficitsMonoamine systemsLife spanMonkeysSimilar patternHumansCortexNeuropathological changesNonhuman primate modelPrimate model
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 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 rangeAntagonistAcquisitionMonkeys
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
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