α 2 -Adrenergic Mechanisms in Prefrontal Cortex Associated with Cognitive Decline in Aged Nonhuman Primates
Abstract
This study provides evidence that the α 2 -adrenergic receptor agonist clonidine ameliorates the cognitive deficits exhibited by aged nonhuman primates through drug actions at α 2 receptors. Furthermore, pharmacological profiles in animals with lesions restricted to the dorsolateral prefrontal cortex indicate that this area may be the site of action for some of clonidine's beneficial effects. These results demonstrate that α-adrenergic systems contribute to cognitive function and suggest a new strategy for treating memory disorders in aged humans.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The beneficial effects of α2-agonists arise from stimulation of postsynaptic α2A-receptors in the PFC.
“Although previous research focused on presynaptic receptor actions, research has established that the beneficial effects of α2-agonists arise from stimulation of postsynaptic α2A-receptors in the PFC (Arnsten and Goldman-Rakic, 1985; Cai et al., 1993).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Arnsten and Goldman-Rakic, 1985
Depletion of noradrenaline or blockade of α2A-receptors in the prefrontal cortex impairs working memory, whereas stimulation of postsynaptic α2A-receptors in the prefrontal cortex improves working memory performance.
“Thus, either depletion of noradrenaline52 or blockade of α2A-receptors in the PFC53 impairs working memory, whereas stimulation of postsynaptic α2A-receptors in the PFC improves working memory performance52,56–58.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [52]
Levels of noradrenaline released during alert, non-stressed waking optimize working memory by engaging α2A-receptors, whereas high levels released during stress impair prefrontal cortex function by stimulating lower-affinity α1-receptors and β1-receptors.
“As shown in FIG. 2, the levels of noradrenaline that are released during alert, non-stressed waking optimize working memory by engaging α2A-receptors52,53, whereas the high levels of noradrenaline that are released during stress impair PFC function by stimulating lower-affinity α1-receptors54 and β1-receptors55.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [52]
Depletion of norepinephrine or blockade of α2A receptors in PFC impairs working memory performance in monkeys.
“Either depletion of NE (35) or blockade of α2A receptors in PFC (36) impairs working memory performance in monkeys, suggesting that endogenous NE plays a large role in strengthening working memory performance.”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [35]
Stimulation of postsynaptic α2A receptors in dorsolateral PFC improves working memory performance.
“Conversely, stimulation of postsynaptic α2A receptors in dorsolateral PFC, e.g., with guanfacine infusions directly into this region, improves working memory performance (35,41–43).”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [35]
Moderate levels of norepinephrine released during alert, nonstressed waking improve working memory performance by engaging postsynaptic α2A receptors, whereas high levels of norepinephrine released during stress impair PFC function via stimulation of lower affinity α1 and β1 receptors.
“Data from studies of monkey dorsolateral PFC demonstrate an inverted-U dose-response: moderate levels of NE released during alert, nonstressed waking improve working memory performance by engaging postsynaptic, α2A receptors (35,36), whereas high levels of NE released during stress impair PFC function via stimulation of lower affinity α1 (37) and β1 receptors (38).”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [35]
Guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α2A-receptors in the PFC, strengthening network connectivity.
“In contrast, guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α2A-receptors in the PFC, strengthening network connectivity.”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [35]
The beneficial effects of α2-AR agonists for higher cognitive function were first discovered in aged monkeys.
“The beneficial effects of α2-AR agonists for higher cognitive function were first discovered in aged monkeys (Arnsten et al., 1988, Arnsten and Goldman-Rakic, 1985)”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Arnsten and Goldman-Rakic, 1985
Beneficial effects of α2-AR agonists on cognition arise from postsynaptic α2A-AR in PFC.
“early research determined that the beneficial effects of α2-AR agonists on cognition arose from postsynaptic receptor actions in the PFC (Arnsten and Goldman-Rakic, 1985, Cai et al., 1993), with a pharmacological profile consistent with the α2A-AR subtype (Arnsten et al., 1988, Arnsten and Leslie, 1991), a finding later confirmed in genetically altered mice (Franowicz et al., 2002).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Arnsten and Goldman-Rakic, 1985
α2-AR agonists improved working memory performance in young monkeys with experimental catecholamine depletion in dlPFC.
“Early studies discovered that α2-AR agonists markedly improved working memory performance in young monkeys with experimental catecholamine depletion in the dlPFC, with effects consistent with actions at post-synaptic receptors in the dlPFC (Arnsten & Goldman-Rakic, 1985).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Arnsten & Goldman-Rakic, 1985
Cites
The cholinergic hypothesis of geriatric memory dysfunction
Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982) · Science · doi:10.1126/science.7046051 · Cited by 5,545 · see citing works
Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & DeLong, M. R. (1982) · Science · doi:10.1126/science.7058341 · Cited by 3,627 · see citing works
SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE
DAVIES, P. (1976) · The Lancet · doi:10.1016/s0140-6736(76)91936-x · Cited by 3,565 · see citing works
Squire, L. R. (1984) · Springer eBooks · doi:10.1007/978-3-642-70094-1_32 · Cited by 2,126 · see citing works
Cognitive Deficit Caused by Regional Depletion of Dopamine in Prefrontal Cortex of Rhesus Monkey
Brozoski, T. J., Brown, R. M., Rosvold, H. E., & Goldman, P. S. (1979) · Science · doi:10.1126/science.112679 · Cited by 1,500 · see citing works
Asher, R. (1961) · The Lancet · doi:10.1016/s0140-6736(61)91217-x · Cited by 1,290 · see citing works
Localization of function within the dorsolateral prefrontal cortex of the rhesus monkey
Goldman, P. S., & Rosvold, H. E. (1970) · Experimental Neurology · doi:10.1016/0014-4886(70)90222-0 · Cited by 581 · see citing works
Assessment in Geriatric Psychopharmacology
Hynie, S. (1986) · Neuropharmacology · doi:10.1016/0028-3908(86)90122-x · Cited by 498 · see citing works
Cell loss in the locus coeruleus in senile dementia of Alzheimer type
Tomlinson, B. E., Irving, D., & Blessed, G. (1981) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(81)90031-9 · Cited by 453 · see citing works
Changes in the Brain Catecholamines in Patients with Dementia of Alzheimer Type
Adolfsson, R., Gottfries, C. G., Roos, B. E., & Winblad, B. G. (1979) · The British Journal of Psychiatry · doi:10.1192/bjp.135.3.216 · Cited by 449 · see citing works
U’PRICHARD, D. C., BECHTEL, W. D., ROUOT, B. M., & SNYDER, S. H. (1979) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)11406-5 · Cited by 384 · see citing works
Goldman, P. S., Rosvold, H. E., Vest, B., & Galkin, T. W. (1971) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0031649 · Cited by 381 · see citing works
Physostigmine and Arecoline: Effects of Intravenous Infusions in Alzheimer Presenile Dementia
CHRISTIE, J. E., Shering, A., Ferguson, J. M., & Glen, A. I. M. (1981) · The British Journal of Psychiatry · doi:10.1192/bjp.138.1.46 · Cited by 360 · see citing works
Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys
Goldman‐Rakic, P. S., & Brown, R. M. (1981) · Neuroscience · doi:10.1016/0306-4522(81)90053-1 · Cited by 357 · see citing works
Self-citationArnsten, A. F. T., & Goldman-Rakic, P. S. (1984) · Brain Research · doi:10.1016/0006-8993(84)90351-2 · Cited by 333 · see citing works
Self-citationAging in the Rhesus Monkey: Debilitating Effects on Short-term Memory
Bartus, R. T., Fleming, D., & Johnson, H. R. (1978) · Journal of Gerontology · doi:10.1093/geronj/33.6.858 · Cited by 284 · see citing works
Iversen, L. L., Rossor, M. N., Reynolds, G. P., Hills, R., Roth, M., Mountjoy, C. Q., Foote, S. L., Morrison, J. H., & Bloom, F. E. (1983) · Neuroscience Letters · doi:10.1016/0304-3940(83)90171-4 · Cited by 264 · see citing works
Neuropathological and biochemical observations on the noradrenergic system in Alzheimer's disease
Perry, E. K., Tomlinson, B. E., Blessed, G., Perry, R. H., Cross, A. J., & Crow, T. J. (1981) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(81)90106-4 · Cited by 171 · see citing works
Memory Deficits in Aged Cebus Monkeys and Facilitation With Central Cholinomimetics
Bartus, R. T., Dean, R. L., & Beer, B. (1980) · Neurobiology of Aging · doi:10.1016/0197-4580(80)90008-1 · Cited by 170 · see citing works
Benzodiazepines attenuate single unit activity in the locus coeruleus
Grant, S. J., Huang, Y. H., & Redmond, D. E. (1980) · Life Sciences · doi:10.1016/0024-3205(80)90389-6 · Cited by 162 · see citing works
McEntee, W. J., & Mair, R. G. (1980) · Annals of Neurology · doi:10.1002/ana.410070513 · Cited by 154 · see citing works
Cross, A. J., Crow, T. J., Johnson, J. A., Perry, E. K., Perry, R. H., Blessed, G., & Tomlinson, B. E. (1984) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(84)90029-7 · Cited by 128 · see citing works
Catecholaminergic neurites in senile plaques in prefrontal cortex of aged nonhuman primates
Kitt, C. A., Struble, R. G., Cork, L. C., Mobley, W. C., Walker, L. C., Joh, T. H., & Price, D. L. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90202-7 · Cited by 81 · see citing works
ALZHEIMER'S DISEASE AS A DISORDER OF ISODENDRITIC CORE
Benton, J. S., Bowen, D. M., Allen, S. J., Haan, E., DAVISON, A. N., Neary, D., Murphy, R., & Snowden, J. S. (1982) · The Lancet · doi:10.1016/s0140-6736(82)91667-1 · Cited by 81 · see citing works
THE LOCUS CAERULEUS IN ALZHETMERʼS DISEASE,
Forno, L. S. (1978) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-197809000-00140 · Cited by 64 · see citing works
Finch, C. E. (1978) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-8893-7_2 · Cited by 55 · see citing works
McGaugh, J. L. (1985) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1985.tb37586.x · Cited by 45 · see citing works
Ward, D. J., & Lea, D. J. (1975) · The Lancet · doi:10.1016/s0140-6736(75)91527-5 · Cited by 43 · see citing works
Mattiace, L. A., McDermott, K., & German, D. C. (1984) · The Society for Neuroscience Abstracts · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Self-citationBerridge, C. W., & Waterhouse, B. D. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00143-7 · Cited by 2,529 · see citing works
Insights into the ageing mind: a view from cognitive neuroscience
Hedden, T., & Gabrieli, J. D. E. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1323 · Cited by 2,223 · see citing works
An application of prefrontal cortex function theory to cognitive aging.
West, R. L. (1996) · Psychological Bulletin · doi:10.1037/0033-2909.120.2.272 · Cited by 2,032 · see citing works
Circuitry of Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory
Goldman‐Rakic, P. S. (1987) · Comprehensive Physiology · doi:10.1002/cphy.cp010509 · Cited by 1,960 · see citing works
The locus coeruleus and noradrenergic modulation of cognition
Sara, S. J. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2573 · Cited by 1,848 · see citing works
Jentsch, J., & Roth, R. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00060-8 · Cited by 1,349 · see citing works
Sensorimotor Gating and Schizophrenia
Braff, D. L. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810140081011 · Cited by 1,312 · see citing works
Miyamoto, S., Duncan, G. E., Marx, C. E., & Lieberman, J. A. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001556 · Cited by 988 · see citing works
Neurobiology of Executive Functions: Catecholamine Influences on Prefrontal Cortical Functions
Arnsten, A. F. T., & Li, B.-M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.08.019 · Cited by 948 · see citing works
Self-citationCoull, J. T. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00011-2 · Cited by 882 · see citing works
Bartus, R. T. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7397 · Cited by 829 · see citing works
Development of Cortical Circuitry and Cognitive Function
Goldman‐Rakic, P. S. (1987) · Child Development · doi:10.2307/1130201 · Cited by 817 · see citing works
Self-citationModafinil: a review of neurochemical actions and effects on cognition
Minzenberg, M. J., & Carter, C. S. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301534 · Cited by 713 · see citing works
Mather, M., Clewett, D., Sakaki, M., & Harley, C. W. (2016) · Behavioral and Brain Sciences · doi:10.1017/s0140525x15000667 · Cited by 695 · see citing works
Keefe, R. S. E., Silva, S. G., Perkins, D. O., & Lieberman, J. A. (1999) · Schizophrenia Bulletin · doi:10.1093/oxfordjournals.schbul.a033374 · Cited by 690 · see citing works
Solanto, M. V. (1998) · Behavioural Brain Research · doi:10.1016/s0166-4328(97)00175-7 · Cited by 677 · see citing works
Wang, M., Ramos, B. P., Paspalas, C. D., Shu, Y., Simen, A., Duque, A., Vijayraghavan, S., Brennan, A., Dudley, A., Nou, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.015 · Cited by 672 · see citing works
Self-citationDo Rats Have Prefrontal Cortex? The Rose-Woolsey-Akert Program Reconsidered
Preuss, T. M. (1995) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.1995.7.1.1 · Cited by 666 · see citing works
Adrenergic pharmacology and cognition: Focus on the prefrontal cortex
Ramos, B. P., & Arnsten, A. F. T. (2007) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2006.11.006 · Cited by 641 · see citing works
Self-citationDiamond, A., & Goldman-Rakic, P. S. (1989) · Experimental Brain Research · doi:10.1007/bf00248277 · Cited by 628 · see citing works
Self-citationFrontal-subcortical circuitry and behavior
Bonelli, R. M., & Cummings, J. L. (2007) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2007.9.2/rbonelli · Cited by 613 · see citing works
Mehta, M. A., Owen, A. M., Sahakian, B. J., Mavaddat, N., Pickard, J. D., & Robbins, T. W. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-06-j0004.2000 · Cited by 608 · see citing works
Catecholamine modulation of prefrontal cortical cognitive function
Arnsten, A. F. T. (1998) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(98)01240-6 · Cited by 608 · see citing works
Self-citationNoradrenergic mechanisms in stress and anxiety: I. preclinical studies
Bremner, J., Krystal, J., Southwick, S., & Charney, D. (1996) · Synapse · doi:10.1002/(sici)1098-2396(199605)23:1 · Cited by 571 · see citing works
Miyamoto, S., Miyake, N., Jarskog, L. F., Fleischhacker, W. W., & Lieberman, J. A. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.47 · Cited by 576 · see citing works
Coull, J. T., Frith, C. D., Frackowiak, R. S. J., & Grasby, P. M. (1996) · Neuropsychologia · doi:10.1016/0028-3932(96)00029-2 · Cited by 566 · see citing works
Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys
Arnsten, A. F. T., Cai, J. X., Murphy, B. L., & Goldman-Rakic, P. S. (1994) · Psychopharmacology · doi:10.1007/bf02245056 · Cited by 566 · see citing works
Self-citationDecker, M. W., & McGaugh, J. L. (1991) · Synapse · doi:10.1002/syn.890070209 · Cited by 524 · see citing works
McMorris, T., & Hale, B. J. (2012) · Brain and Cognition · doi:10.1016/j.bandc.2012.09.001 · Cited by 516 · see citing works
Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks
Arnsten, A. F. T. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.027 · Cited by 493 · see citing works
Self-citationCatecholamine regulation of the prefrontal cortex
Arnsten, A. F. T. (1997) · Journal of Psychopharmacology · doi:10.1177/026988119701100208 · Cited by 489 · see citing works
Self-citationExtrathalamic Modulation of Cortical Function
Foote, S. L., & Morrison, J. (1987) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.10.030187.000435 · Cited by 480 · see citing works
Royall, D. R., Lauterbach, E. C., Cummings, J. L., Reeve, A., Rummans, T. A., Kaufer, D., LaFrance, W. C., Jr., & Coffey, C. E. (2002) · Journal of Neuropsychiatry · doi:10.1176/jnp.14.4.377 · Cited by 790 · see citing works
Stimulants: Therapeutic Actions in ADHD
Arnsten, A. F. T. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301164 · Cited by 473 · see citing works
Self-citationArnsten, A. F. T. (1996) · Archives of General Psychiatry · doi:10.1001/archpsyc.1996.01830050084013 · Cited by 458 · see citing works
Self-citationRole of the lateral prefrontal cortex in executive behavioral control.
Tanji, J., & Hoshi, E. (2008) · Physiological Reviews · doi:10.1152/physrev.00014.2007 · Cited by 495 · see citing works
Arnsten, A., Cai, J., & Goldman-Rakic, P. (1988) · The Journal of Neuroscience · doi:10.1523/jneurosci.08-11-04287.1988 · Cited by 391 · see citing works
Self-citationEffects of methylphenidate on spatial working memory and planning in healthy young adults
Elliott, R., Sahakian, B. J., Matthews, K., Bannerjea, A., Rimmer, J., & Robbins, T. W. (1997) · Psychopharmacology · doi:10.1007/s002130050284 · Cited by 389 · see citing works
Arnsten, A. F. T., & Pliszka, S. R. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.01.020 · Cited by 383 · see citing works
Self-citationArnsten, A. F. T. (2009) · CNS Drugs · doi:10.2165/00023210-200923000-00005 · Cited by 371 · see citing works
Self-citationNeuroplasticity of Neocortical Circuits in Schizophrenia
Lewis, D. A., & González‐Burgos, G. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301563 · Cited by 362 · see citing works
Nieuwenhuis, S., Ridderinkhof, K. R., Talsma, D., COLES, M. G. H., Holroyd, C. B., Kok, A., & van der Molen, M. W. (2002) · Cognitive Affective & Behavioral Neuroscience · doi:10.3758/cabn.2.1.19 · Cited by 348 · see citing works
Arnsten, A. F. T., Scahill, L. D., & Findling, R. L. (2007) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2006.0098 · Cited by 311 · see citing works
Self-citationAn Open Trial of Guanfacine in the Treatment of Attention-Deficit Hyperactivity Disorder
Hunt, R. D., Arnsten, A. F. T., & Asbell, M. D. (1995) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199501000-00013 · Cited by 308 · see citing works
Self-citationPatterns of cognitive decline in aged rhesus monkeys
Herndon, J. G., Moss, M. B., Rosene, D. L., & Killiany, R. (1997) · Behavioural Brain Research · doi:10.1016/s0166-4328(96)02256-5 · Cited by 290 · see citing works
Crofts, H. S. (2001) · Cerebral Cortex · doi:10.1093/cercor/11.11.1015 · Cited by 284 · see citing works
Evidence for task-dependent memory dysfunction in the aged monkey
Rapp, P. R., & Amaral, D. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-10-03568.1989 · Cited by 277 · see citing works
Neuropsychology of Early-treated Phenylketonuria: Specific Executive Function Deficits
Welsh, M. C., Pennington, B. F., Ozonoff, S. J., Rouse, B. M., & McCabe, E. R. B. (1990) · Child Development · doi:10.1111/j.1467-8624.1990.tb03560.x · Cited by 277 · see citing works
Brennan, A. R., & Arnsten, A. F. T. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1417.007 · Cited by 267 · see citing works
Self-citationAged monkeys exhibit behavioral deficits indicative of widespread cerebral dysfunction
Bachevalier, J., Landis, L. S., Walker, L. C., Brickson, M., Mishkin, M., Price, D. L., & Cork, L. C. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90048-o · Cited by 264 · see citing works
Role of Prefrontal Persistent Activity in Working Memory
Riley, M. R., & Constantinidis, C. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00181 · Cited by 251 · see citing works
Chronic exposure to low doses of MPTP. I. Cognitive deficits in motor asymptomatic monkeys
Schneider, J. S., & Kovelowski, C. J. (1990) · Brain Research · doi:10.1016/0006-8993(90)90069-n · Cited by 246 · see citing works
Animal models of attention-deficit hyperactivity disorder
Russell, V. A., Sagvolden, T., & Johansen, E. B. (2005) · Behavioral and Brain Functions · doi:10.1186/1744-9081-1-9 · Cited by 234 · see citing works
Working memory, attention, and salience in active inference
Parr, T., & Friston, K. J. (2017) · Scientific Reports · doi:10.1038/s41598-017-15249-0 · Cited by 226 · see citing works
Through the looking glass: Differential noradenergic modulation of prefrontal cortical function
Arnsten, A. F. T. (2000) · Neural Plasticity · doi:10.1155/np.2000.133 · Cited by 229 · see citing works
Self-citationCollins, P., Roberts, A., Dias, R. S., Everitt, B. J., & Robbins, T. W. (1998) · Journal of Cognitive Neuroscience · doi:10.1162/089892998562771 · Cited by 229 · see citing works
Growth hormone, insulin-like growth factor-1 and the aging brain
Ashpole, N. M., Sanders, J. E., Hodges, E. L., Han, Y., & Sonntag, W. E. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.10.002 · Cited by 226 · see citing works
Rostral locus coeruleus integrity is associated with better memory performance in older adults
Dahl, M. J., Mather, M., Düzel, S., Bodammer, N., Lindenberger, U., Kühn, S., & Werkle‐Bergner, M. (2019) · Nature Human Behaviour · doi:10.1038/s41562-019-0715-2 · Cited by 214 · see citing works
Catecholamines and the covert orientation of attention in humans
Clark, C. R., Geffen, G. M., & Geffen, L. B. (1989) · Neuropsychologia · doi:10.1016/0028-3932(89)90166-8 · Cited by 222 · see citing works
Perikaryal and synaptic localization ofα2A-adrenergic receptor-like immunoreactivity
Aoki, C. J., Go, C.-G., Venkatesan, C., & Kurose, H. (1994) · Brain Research · doi:10.1016/0006-8993(94)91782-5 · Cited by 221 · see citing works
Dysregulation of Protein Kinase A Signaling in the Aged Prefrontal Cortex
Ramos, B. P., Birnbaum, S. G., Lindenmayer, I., Newton, S. S., Duman, R. S., & Arnsten, A. F. T. (2003) · Neuron · doi:10.1016/s0896-6273(03)00694-9 · Cited by 218 · see citing works
Self-citationModulators in concert for cognition: Modulator interactions in the prefrontal cortex
Briand, L. A., Gritton, H., Howe, W. M., Young, D. A., & Sarter, M. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.06.007 · Cited by 216 · see citing works
ADHD and the Prefrontal Cortex
Arnsten, A. F. T. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2009.01.018 · Cited by 220 · see citing works
Self-citationSwanson, C. J., Perry, K. W., Koch-Krueger, S., Katner, J., Svensson, K. A., & Bymaster, F. P. (2006) · Neuropharmacology · doi:10.1016/j.neuropharm.2005.11.022 · Cited by 214 · see citing works
Noradrenergic dysfunction in Alzheimer's disease
Gannon, M. A., Che, P., Chen, Y., Jiao, K., Roberson, E. D., & Wang, Q. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00220 · Cited by 211 · see citing works
The role of noradrenaline in cognition and cognitive disorders
Holland, N., Robbins, T. W., & Rowe, J. B. (2021) · Brain · doi:10.1093/brain/awab111 · Cited by 201 · see citing works
Noradrenergic Modulation of Cognition in Health and Disease
Borodovitsyna, O., Flamini, M. D., & Chandler, D. J. (2017) · Neural Plasticity · doi:10.1155/2017/6031478 · Cited by 210 · see citing works
Cools, R., & Arnsten, A. F. T. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01100-8 · Cited by 206 · see citing works
Self-citationArnsten, A. F. T. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhm033 · Cited by 200 · see citing works
Self-citationTang, Y. C. (2003) · Cerebral Cortex · doi:10.1093/cercor/bhg121 · Cited by 197 · see citing works
Arnsten, A. F. T. (2000) · Progress in brain research · doi:10.1016/s0079-6123(00)26014-7 · Cited by 194 · see citing works
Self-citationGuanfacine, But Not Clonidine, Improves Planning and Working Memory Performance in Humans
Jäkälä, P. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00127-4 · Cited by 189 · see citing works
Gallagher, M., & Nicolle, M. M. (1993) · Behavioural Brain Research · doi:10.1016/0166-4328(93)90131-9 · Cited by 189 · see citing works
Cotman, C. W., & Head, E. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15413 · Cited by 188 · see citing works
Li, B.-M., & Mei, Z.-T. (1994) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(05)80034-2 · Cited by 186 · see citing works
Impact of aging brain circuits on cognition
Samson, R. D., & Barnes, C. A. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12183 · Cited by 184 · see citing works
Franowicz, J. S., Kessler, L. E., Borja, C. M. D., Kobilka, B. K., Limbird, L. E., & Arnsten, A. F. T. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-19-08771.2002 · Cited by 185 · see citing works
Self-citationEffects of aging on visual recognition memory in the rhesus monkey
Moss, M. B., Rosene, D. L., & Peters, A. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80103-9 · Cited by 181 · see citing works
Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part I
Sarter, M. F., Hagan, J. J., & Dudchenko, P. A. (1992) · Psychopharmacology · doi:10.1007/bf02245132 · Cited by 181 · see citing works
Animal models of attention-deficit hyperactivity disorder.
Davids, E., Zhang, K., Tarazi, F. I., & Baldessarini, R. J. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00274-6 · Cited by 250 · see citing works
Visual-discrimination learning ability and β-amyloid accumulation in the dog
Head, E., Callahan, H., Muggenburg, B. A., Cotman, C. W., & Milgram, N. W. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00084-0 · Cited by 176 · see citing works
Hoshi, E. (2005) · Neuroscience Research · doi:10.1016/j.neures.2005.10.013 · Cited by 175 · see citing works
Neuroprotective effects of huperzine A: New therapeutic targets for neurodegenerative disease
Zhang, H. Y., & Tang, X. C. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.10.004 · Cited by 174 · see citing works
Hämmerer, D., Callaghan, M. F., Hopkins, A. K., Kosciessa, J. Q., Betts, M. J., Cárdenas‐Blanco, A., Kanowski, M., Weiskopf, N., Dayan, P., Dolan, R. J., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1712268115 · Cited by 159 · see citing works
Arnsten, A. F. T., & Contant, T. A. (1992) · Psychopharmacology · doi:10.1007/bf02245302 · Cited by 168 · see citing works
Self-citationFallon, J. H., & Loughlin, S. E. (1932) · Cerebral cortex · doi:10.1007/978-1-4615-6616-8_2 · Cited by 165 · see citing works
Kalaria, R. N., Andorn, A. C., Tabaton, M., Whitehouse, P. J., Harik, S. I., & Unnerstall, J. R. (1989) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1989.tb09242.x · Cited by 163 · see citing works
Li, B. (1999) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00070-6 · Cited by 162 · see citing works
Age differences in recognition memory of the rhesus monkey (Macaca mulatta)
Presty, S. K., Bachevalier, J., Walker, L. C., Struble, R. G., Price, D. L., Mishkin, M., & Cork, L. C. (1987) · Neurobiology of Aging · doi:10.1016/0197-4580(87)90038-8 · Cited by 162 · see citing works
The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing
Sonntag, W. E., Lynch, C. D., Thornton, P. L., Khan, A. S., Bennett, S. A., & Ingram, R. L. (2000) · Journal of Anatomy · doi:10.1046/j.1469-7580.2000.19740575.x · Cited by 160 · see citing works
Exercise and Cognitive Function
Loprinzi, P. D., & Kane, C. (2015) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2014.12.023 · Cited by 159 · see citing works
A canine model of human aging and Alzheimer's disease
Head, E. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.03.016 · Cited by 160 · see citing works
Mao, Z.-M., Arnsten, A. F. T., & Li, B.-M. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00139-0 · Cited by 156 · see citing works
Self-citationNoradrenergically Mediated Plasticity in a Human Attentional Neuronal Network
Coull, J. T., Büchel, C., Friston, K. J., & Frith, C. (1999) · NeuroImage · doi:10.1006/nimg.1999.0513 · Cited by 156 · see citing works
11. The effects of positive affect and arousal on working memory and executive attention
Ashby, F. G., Valentin, V. V., & Turken, A. U. (2002) · Advances in consciousness research · doi:10.1075/aicr.44.11ash · Cited by 155 · see citing works
Spatial learning and memory as a function of age in the dog.
Head, E., Mehta, R., Hartley, J., Kameka, M., Cummings, B. J., Cotman, C. W., Ruehl, W. W., & Milgram, N. W. (1995) · Behavioral Neuroscience · doi:10.1037/0735-7044.109.5.851 · Cited by 155 · see citing works
A post-mortem study of noradrenergic, serotonergic and GABAergic neurons in Alzheimer's disease
Reinikainen, K. J., Paljärvi, L., Huuskonen, M., Soininen, H. S., Laakso, M., & Riekkinen, P. J. (1988) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(88)90179-7 · Cited by 154 · see citing works
Metabolomic changes in autopsy‐confirmed Alzheimer's disease
Kaddurah-Daouk, R. F., Rozen, S., Matson, W. R., Han, X., Hulette, C. M., Burke, J. R., Doraiswamy, P. M., & Welsh-Bohmer, K. A. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.06.001 · Cited by 145 · see citing works
The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys
Ramos, B. P., Colgan, L., Nou, E., Ovadia, S., Wilson, S. R., & Arnsten, A. F. T. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.05.022 · Cited by 147 · see citing works
Self-citation
- Authors
- Arnsten, A. F. T., & Goldman-Rakic, P. S.
- Affiliations
- Yale University (US)
- Section of Neuroanatomy, Yale Medical School, New Haven, Connecticut 06510
- ORCID
- Arnsten, Amy F. T.
- Venue
- Science
- Published
- 1985-12-13
- Volume
- 230
- Issue
- 4731
- Pages
- 1273-1276
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2000247756
- Cited by
- 549
- References
- 29
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 13 · 2017: 7 · 2016: 11 · 2015: 15 · 2014: 7 · 2013: 14 · 2012: 10
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (NIMH 00298, NIMH-08641, NIMH#38546)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- alpha2-adrenoceptors, clonidine, prefrontal cortex, cognitive decline, aging, non-human primates, memory disorders, adrenergic system, cognitive impairment
- MeSH terms
- Aging, Animals, Cerebral Cortex, Clonidine, Cognition, Female, Hydroxydopamines, Macaca mulatta, Memory, Prazosin, Receptors, Adrenergic, alpha, Yohimbine, Oxidopamine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
