2024
Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function
Wiseman R, Bigos K, Arnsten A, Slusher B. Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function. Advances In Pharmacology 2024 DOI: 10.1016/bs.apha.2024.10.018.Peer-Reviewed Original ResearchN-acetylaspartyl glutamateGlutamate carboxypeptidase IICognitive deficitsCognitive functionDorsolateral prefrontal cortex of primatesPrefrontal cortex of primatesHigher order cognitive processesDorsolateral prefrontal cortexMetabotropic glutamate receptor 3Inhibition of glutamate carboxypeptidase IIImprove cognitive deficitsEnhance cognitive functionImprove cognitive performanceEnzyme glutamate carboxypeptidase IIGlutamate receptor 3Executive functionCortex of primatesMGlu3 receptorsCarboxypeptidase IICognitive performanceCognitive processesPersistent neuronal firingClinical populationsNeuronal firingClinical work
2015
Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive function
Berridge C, Arnsten A. Catecholamine mechanisms in the prefrontal cortex: proven strategies for enhancing higher cognitive function. Current Opinion In Behavioral Sciences 2015, 4: 33-40. DOI: 10.1016/j.cobeha.2015.01.002.Peer-Reviewed Original ResearchAttention deficit hyperactivity disorderPharmacological treatmentCognitive dysfunctionPrefrontal cognitive dysfunctionCognition-enhancing effectsMultiple psychiatric disordersSpecific intracellular pathwaysDeficit hyperactivity disorderPrefrontal catecholaminesClinical efficacyCatecholamine mechanismsADHD medicationNovel medicationsReceptor mechanismsPrefrontal cognitionPsychiatric disordersCatecholamine receptorsCatecholamine modulationHigher cognitive functionsCognitive functionPrefrontal cortexHyperactivity disorderImproved treatmentIntracellular pathwaysKey modulator
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
2012
Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale.
Arnsten AF, Jin LE. Guanfacine for the treatment of cognitive disorders: a century of discoveries at Yale. The Yale Journal Of Biology And Medicine 2012, 85: 45-58. PMID: 22461743, PMCID: PMC3313539.Peer-Reviewed Original ResearchConceptsAttention deficit hyperactivity disorderPrefrontal cortexCognitive disordersHigher-order cognitive abilitiesDeficit hyperactivity disorderPFC cognitive functionCognitive abilitiesHyperactivity disorderCognitive functionMemory functionPFC functionAgonist guanfacineBrain regionsGuanfacineRecent researchNeurobiologyYale Medical SchoolCentury of discoveryDisordersTherapeutic targetTourette syndromePostsynaptic spinesEmotionsMemorySyndrome
2009
5.3 Dopamine’s Influence on Prefrontal Cortical Cognition: Actions and Circuits in Behaving Primates
Arnsten A, Vijayraghavan S, Wang M, Gamo N, Paspalas C. 5.3 Dopamine’s Influence on Prefrontal Cortical Cognition: Actions and Circuits in Behaving Primates. 2009, 230-248. DOI: 10.1093/acprof:oso/9780195373035.003.0016.Peer-Reviewed Original Research
2006
The effects of sex and hormonal status on restraint-stress-induced working memory impairment
Shansky RM, Rubinow K, Brennan A, Arnsten A. The effects of sex and hormonal status on restraint-stress-induced working memory impairment. Behavioral And Brain Functions 2006, 2: 8. PMID: 16522198, PMCID: PMC1420310, DOI: 10.1186/1744-9081-2-8.Peer-Reviewed Original ResearchRestraint stressStress-related disordersPrefrontal cortexFemale ratsHormonal statusCognitive functionPFC cognitive functionAcute restraint stressHigh estrogen levelsMajor depressive disorderMinutes of restraintMethodsThe present studyDendritic remodelingEstrogen levelsDepressive disorderMale ratsPharmacological stressorHormonal influencesMemory impairmentHippocampal functionSignificant impairmentNeuronal morphologyConclusionThese resultsEstrus phaseOestrous cycle
2000
Dopaminergic and Noradrenergic Influences on Cognitive Functions Mediated by Prefrontal Cortex
Arnsten A. Dopaminergic and Noradrenergic Influences on Cognitive Functions Mediated by Prefrontal Cortex. 2000, 185-208. DOI: 10.1093/oso/9780195133714.003.0008.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 stressorα-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
Catecholamine modulation of prefrontal cortical cognitive function
Arnsten A. Catecholamine modulation of prefrontal cortical cognitive function. Trends In Cognitive Sciences 1998, 2: 436-447. PMID: 21227275, DOI: 10.1016/s1364-6613(98)01240-6.Peer-Reviewed Original ResearchAttention deficit hyperactivity disorderPrefrontal cortexCognitive functionPrefrontal cortical cognitive functionUncontrollable stressCortical cognitive functionsWorking Memory FunctionDeficit hyperactivity disorderHyperactivity disorderPFC functionPFC dysfunctionNormal agingCognitive disordersCatecholamine modulationDopamine systemNeurochemical influencesMental disordersNeuropsychiatric disordersDisordersEnvironmental cuesCuesNeuromodulatory inputsMemoryFresh understandingHigh levels
1997
Clozapine Reverses the Spatial Working Memory Deficits Induced by FG7142 in Monkeys
Murphy B, Roth R, Arnsten A. Clozapine Reverses the Spatial Working Memory Deficits Induced by FG7142 in Monkeys. Neuropsychopharmacology 1997, 16: 433-437. PMID: 9165499, DOI: 10.1016/s0893-133x(97)00019-5.Peer-Reviewed Original ResearchConceptsMemory deficitsClozapine dosesCognitive deficitsDA receptor stimulationLow clozapine dosesDose-related impairmentPFC cognitive deficitsSpatial Working Memory DeficitsClozapine pretreatmentClozapine reversesAtypical neurolepticsPharmacological stressorDopamine dysregulationReceptor stimulationCognitive functionNonhuman primatesClinical rangeDosesWorking Memory DeficitsClozapineMonkeysDeficitsFG7142SchizophreniaCurrent studyCatecholamine regulation of the prefrontal cortex
Arnsten A. Catecholamine regulation of the prefrontal cortex. Journal Of Psychopharmacology 1997, 11: 151-162. PMID: 9208378, DOI: 10.1177/026988119701100208.Peer-Reviewed Original ResearchConceptsPrefrontal cortexAdrenergic receptorsAlpha-1 adrenergic receptorsPFC functionPFC cognitive functionAlpha 2A-adrenergic receptorD1 receptor stimulationTreatment of disordersCatecholamine regulationCatecholamine releaseDA stimulationCatecholamine stimulationD2 familyProminent symptomReceptor stimulationModulatory influencePFC dysfunctionCognitive functionSubcortical structuresReview evidenceDetrimental actionsCatecholamines dopamineReceptorsStimulationNorepinephrineThe 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
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
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