2024
Combined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury
Khasnavis S, Belliveau T, Arnsten A, Fesharaki-Zadeh A. Combined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury. Neurotrauma Reports 2024, 5: 226-231. PMID: 38524728, PMCID: PMC10960163, DOI: 10.1089/neur.2023.0124.Peer-Reviewed Original ResearchTreatment of cognitive deficitsTraumatic brain injuryExecutive functionCognitive deficitsTraumatic brain injury clinicEfficacy of guanfacinePre-frontal cortexBrain injuryTreat traumatic brain injuryBehavioral therapyNeuropsychological testsCognitive symptomsCognitive changesPlacebo-controlled trialProcessing speedGuanfacineCortical functionOpen-label useApproved medicationsPersonsPost-treatmentDeficitsTraumatizationN-acetylcysteineMTBIInhibition 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
2023
Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”
Fesharaki-Zadeh A, Lowe N, Arnsten A. Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”. Neuroimmunology Reports 2023, 3: 100154. DOI: 10.1016/j.nerep.2022.100154.Peer-Reviewed Original ResearchN-acetylcysteineCognitive deficitsΑ2A-adrenoceptor agonistsPrefrontal cortexCOVID19 infectionPlacebo-controlled trialOpen-label treatmentCommon side effectsExecutive functionPFC connectionsBrain fogAcid blockadeLabel treatmentHypotensive episodesGuanfacine treatmentNMDA receptorsPatient brieflySide effectsClinical experienceGuanfacineCognitive impairmentPatientsPrefrontal connectivityDemonstrate efficacyPrefrontal function
2019
Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease
Arnsten AFT, Datta D, Leslie S, Yang ST, Wang M, Nairn AC. Alzheimer’s-like pathology in aging rhesus macaques: Unique opportunity to study the etiology and treatment of Alzheimer’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 26230-26238. PMID: 31871209, PMCID: PMC6936707, DOI: 10.1073/pnas.1903671116.Peer-Reviewed Original ResearchTau pathologyAlzheimer's diseaseAssociation cortexTau phosphorylationMouse modelRhesus monkeysSignificant amyloid pathologyAlzheimer-like pathologyPrefrontal association cortexTau phosphorylation statePrimary sensory cortexOnset Alzheimer's diseasePrecursor protein cleavagePreventive therapyAmyloid pathologyCalcium dysregulationEarly stage degenerationPhosphorylated tauPrecipitating factorsSensory cortexCognitive deficitsAD researchRhesus macaquesPathologyCortex
2015
Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders
Arnsten AF, Wang M, Paspalas CD. Dopamine’s Actions in Primate Prefrontal Cortex: Challenges for Treating Cognitive Disorders. Pharmacological Reviews 2015, 67: 681-696. PMID: 26106146, PMCID: PMC4485014, DOI: 10.1124/pr.115.010512.Peer-Reviewed Original ResearchConceptsCell firingPyramidal cell dendritesD2 receptor familyFrontal eye fieldPrimate prefrontal cortexGABA interneuronsCortical dopamineDopamine actionGlutamate releaseEndogenous dopamineDA cellsCell dendritesD1R agonistDendritic spinesCognitive disordersOrbital PFCEye fieldPositive symptomsLikely projectResponse cellsCognitive deficitsPrefrontal cortexStimulation speedFeedback neuronsD1R
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 findingsMonkeys
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 stressorAge-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
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 study
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
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