The DOI matches its Crossref record; 66 of the 68 references it cites were found in a registry or an index.
The Beta-1 Adrenergic Antagonist, Betaxolol, Improves Working Memory Performance in Rats and Monkeys
Abstract
Background Previous studies have indicated that beta adrenergic receptor stimulation has no effect on the cognitive functioning of the prefrontal cortex (PFC). Blockade of beta-1 and beta-2 receptors in the PFC with the mixed beta-1/beta-2 antagonist, propanolol, had no effect on spatial working memory performance. However, more selective blockade of beta-1 or beta-2 receptors might show efficacy if the two receptors have opposite effects on PFC function. The current study examined the effects of the selective beta-1 antagonist, betaxolol, on working memory in rats and monkeys. Methods In rats, betaxolol (.0011-1.11 microg/.5 microL) was infused into the PFC 5 min before delayed alternation testing. Monkeys were systemically injected with betaxolol (.0000011-.11 mg/kg) 2 hours before delayed response testing. Results Betaxolol produced a dose-related improvement in working memory performance following either direct PFC infusion in rats, or systemic administration in monkeys. However, some aged monkeys developed serious pancreatic problems over the course of this study. Conclusions These findings suggest that endogenous activation of the beta-1 adrenergic receptor impairs PFC cognitive function. These results may have therapeutic relevance to post-traumatic stress disorder or other disorders with excessive noradrenergic activity and PFC dysfunction. Pancreatic side effects in aged subjects taking betaxolol warrants further investigation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“Studies in animals indicate that NE engages predominantly α2-receptors in the PFC when the subject is alert and interested (Li and Mei, 1994), while actions at α1-receptors and possibly β-receptors are predominant under stressful conditions (Birnbaum et al., 2004; Ramos et al., 2005).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Ramos et al., 2005
In the citing paper
“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 [55]
In the citing paper
“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 [38]
In the citing paper
“Norepinephrine may also drive cAMP signaling via the β1-AR61, although this pathway requires further study.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [61]
Citations
Cites
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
Principles of Frontal Lobe Function
Stuss, D. T. (2002) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195134971.001.0001 · Cited by 1,725
β-Adrenergic activation and memory for emotional events
Cahill, L., Prins, B., Weber, M., & McGaugh, J. L. (1994) · Nature · doi:10.1038/371702a0 · Cited by 1,271
Zahrt, J., Taylor, J. R., Mathew, R. G., & Arnsten, A. F. T. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-21-08528.1997 · Cited by 796
Self-citationRaskind, M. A., Peskind, E. R., Kanter, E. D., Petrie, E. C., Radant, A. D., Thompson, C. E., Dobie, D. J., Hoff, D., Rein, R. J., Straits-Tröster, K. A., et al. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.2.371 · Cited by 607
Murphy, B. L., Arnsten, A. F., Goldman-Rakic, P. S., & Roth, R. H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.3.1325 · Cited by 590
Self-citationPrefrontal cortex and episodic memory retrieval mode
Lepage, M., Ghaffar, O., Nyberg, L. H., & Tulving, E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.1.506 · Cited by 583
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
Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder
Southwick, S. M., Bremner, J. D., Rasmusson, A., Morgan, C. A., Arnsten, A., & Charney, D. S. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00219-x · Cited by 573
Self-citationBasal cortisol levels and cognitive deficits in human aging
Lupien, S., Lecours, A., Lussier, I., Schwartz, G., Nair, N., & Meaney, M. (1994) · The Journal of Neuroscience · doi:10.1523/jneurosci.14-05-02893.1994 · Cited by 566
Principles of frontal lobe function
Jellinger, K. A. (2003) · European Journal of Neurology · doi:10.1046/j.1468-1331.2003.00507_2.x · Cited by 562
LUPIEN, S. J., Gillin, C. J., & Hauger, R. L. (1999) · Behavioral Neuroscience · doi:10.1037//0735-7044.113.3.420 · Cited by 556
Arnsten, A. F. T., & Goldman-Rakic, P. S. (1985) · Science · doi:10.1126/science.2999977 · Cited by 549
Self-citationPrefrontal regions involved in keeping information in and out of mind
Bunge, S. A. (2001) · Brain · doi:10.1093/brain/124.10.2074 · Cited by 528
Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma
Vaiva, G., Ducrocq, F., Jezequel, K., Averland, B., Lestavel, P., Brunet, A., & Marmar, C. R. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00412-8 · Cited by 499
Finlay, J. M., Zigmond, M. J., & Abercrombie, E. D. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00331-x · Cited by 434
The Physicians' Desk Reference
Cohen, J. S. (1996) · Archives of Internal Medicine · doi:10.1001/archinte.1996.00440120021003 · Cited by 430
A Distinct Role for Norepinephrine in Memory Retrieval
Murchison, C., Zhang, X., Zhang, W., Ouyang, M., Lee, A., & THOMAS, S. A. (2004) · Cell · doi:10.1016/s0092-8674(04)00259-4 · Cited by 421
Arnsten, A., Cai, J., & Goldman-Rakic, P. (1988) · The Journal of Neuroscience · doi:10.1523/jneurosci.08-11-04287.1988 · Cited by 391
Self-citationGoldstein, L. E., Rasmusson, A. M., Bunney, B. S., & Roth, R. H. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-15-04787.1996 · Cited by 387
Medial temporal lesions in monkeys impair memory on a variety of tasks sensitive to human amnesia.
Zola-Morgan, S. M., & Squire, L. R. (1985) · Behavioral Neuroscience · doi:10.1037//0735-7044.99.1.22 · Cited by 367
Quantitative autoradiography of beta 1- and beta 2-adrenergic receptors in rat brain.
Rainbow, T. C., Parsons, B., & Wolfe, B. B. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.5.1585 · Cited by 351
Roozendaal, B., McReynolds, J. R., & McGaugh, J. L. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4664-03.2004 · Cited by 327
Hypertension and the Brain: Vulnerability of the Prefrontal Regions and Executive Functions.
Raz, N., Rodrigue, K. M., & Acker, J. D. (2003) · Behavioral Neuroscience · doi:10.1037/0735-7044.117.6.1169 · Cited by 312
Goldman-Rakic, P. S., Lidow, M. S., & Gallager, D. W. (1990) · Journal of Neuroscience · doi:10.1523/jneurosci.10-07-02125.1990 · Cited by 311
Noradrenergic enhancement of long-term potentiation at mossy fiber synapses in the hippocampus
Hopkins, W. F., & Johnston, D. (1988) · Journal of Neurophysiology · doi:10.1152/jn.1988.59.2.667 · Cited by 310
Cahill, L., & McGaugh, J. L. (1996) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(96)80078-x · Cited by 301
Roozendaal, B., Hahn, E. L., Nathan, S. V., de Quervain, D. J.-F., & McGaugh, J. L. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.2574-04.2004 · Cited by 301
Bremner, J. D. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830150070011 · Cited by 299
Functional role of the prefrontal cortex in retrieval of memories: a PET study
Kapur, S., Craik, F. I. M., Jones, C., Brown, G. M., Houle, S., & Tulving, E. (1995) · Neuroreport · doi:10.1097/00001756-199510020-00014 · Cited by 295
Birnbaum, S., Gobeske, K. T., Auerbach, J., Taylor, J. R., & Arnsten, A. F. T. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00138-9 · Cited by 281
Self-citationEvidence 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 274
α-1 noradrenergic receptor stimulation impairs prefrontal cortical cognitive function
Arnsten, A. F. T., Mathew, R., Ubriani, R., Taylor, J. R., & Li, B.-M. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00296-0 · Cited by 245
Self-citationDysregulation 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
Self-citationNicholas, A. P., Pieribone, V. A., & Hökfelt, T. G. M. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90148-9 · Cited by 210
Noradrenergic Innervation of Cerebral Cortex: Widespread Effects of Local Cortical Lesions
Morrison, J. H., Molliver, M. E., & Grzanna, R. (1979) · Science · doi:10.1126/science.451605 · Cited by 210
Waterhouse, B. D., Moises, H. C., & Woodward, D. J. (1980) · Experimental Neurology · doi:10.1016/0014-4886(80)90141-7 · Cited by 209
Arnsten, A. F. T. (2000) · Progress in brain research · doi:10.1016/s0079-6123(00)26014-7 · Cited by 198
Self-citationLi, B.-M., & Mei, Z.-T. (1994) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(05)80034-2 · Cited by 186
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
Self-citationMorrison, J. H., Molliver, M. E., Grzanna, R., & Coyle, J. T. (1981) · Neuroscience · doi:10.1016/0306-4522(81)90051-8 · Cited by 167
Friedman, J. I., Adler, D. N., & Davis, K. L. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00232-2 · Cited by 147
Selective ablations within the prefrontal cortex of the rat and performance of delayed alternation
Larsen, J., & Divac, I. (1978) · Physiological Psychology · doi:10.3758/bf03326684 · Cited by 146
Stress-level cortisol treatment impairs inhibitory control of behavior in monkeys
Lyons, D. M., Lopez, J. M., Yang, C., & Schatzberg, A. F. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-20-07816.2000 · Cited by 144
Involvement of α1-adrenoceptors in the basolateral amygdala in modulation of memory storage
Ferry, B., Roozendaal, B., & McGaugh, J. L. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00169-7 · Cited by 142
Roozendaal, B., de Quervain, D. J. ‐., Schelling, G., & McGaugh, J. L. (2003) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2003.10.001 · Cited by 129
Sessler, F. M., Mouradian, R., Cheng, J.-T., Yeh, H. H., Liu, W., & Waterhouse, B. D. (1989) · Brain Research · doi:10.1016/0006-8993(89)91132-3 · Cited by 122
Taylor, J. R., Birnbaum, S., Ubriani, R., & Arnsten, A. F. T. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-18-j0001.1999 · Cited by 120
Self-citationExpression of β3‐adrenoceptor mRNA in rat brain
Summers, R. J., Papaioannou, M., Harris, S., & Evans, B. A. (1995) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1995.tb17205.x · Cited by 118
Effects of Hypertension on Attention, Memory, and Executive Function in Older Adults.
Saxby, B. K., Harrington, F., McKeith, I. G., Wesnes, K. A., & Ford, G. A. (2003) · Health Psychology · doi:10.1037/0278-6133.22.6.587 · Cited by 117
Sandok, B. A., & Whisnant, J. P. (1974) · PubMed · Cited by 102
Ji, J., Wang, X., & Li, B. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02620.x · Cited by 92
The ageing brain: normal and abnormal memory
The American Association for Research into Nervous and Mental Diseases, & Albert, M. (1997) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1997.0152 · Cited by 82
Beresford, R., & Heel, R. C. (1986) · Drugs · doi:10.2165/00003495-198631010-00002 · Cited by 63
Berridge, C. W., Bolen, S. J., Manley, M. S., & Foote, S. L. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-21-07010.1996 · Cited by 59
Deficient Spatial Memory Induced by Blockade of Beta-Adrenoceptors in the Hippocampal CA1 Region.
Ji, J. Z., Zhang, X. H., & Li, B.-M. (2003) · Behavioral Neuroscience · doi:10.1037/0735-7044.117.6.1378 · Cited by 55
Impairment of executive function induced by hypertension in the Rhesus monkey (Macaca mulatta).
Moore, T. L., Killiany, R., Rosene, D. L., Prusty, S., Hollander, W., & Moss, M. B. (2002) · Behavioral Neuroscience · doi:10.1037//0735-7044.116.3.387 · Cited by 36
Tevaearai, H. T., & Koch, W. J. (2004) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2004.07.002 · Cited by 30
Whalley, L. J. (2001) · Cited by 28
Neurodegenerative and age-related changes in structure and function of cerebral cortex
Peters, A., & Morrison, J. H. (1999) · Medical Entomology and Zoology · Cited by 25
Low-dose α/β blockade in the treatment of essential hypertension
Mann, S. J. (2001) · American Journal of Hypertension · doi:10.1016/s0895-7061(00)01302-9 · Cited by 21
Regional brain monoamine levels and utilization in middle-aged rats
Hadfield, M. G., & Milio, C. (1990) · Life Sciences · doi:10.1016/0024-3205(90)90036-q · Cited by 17
Age-Related Cognitive Deficits and Neurotransmitters
Arnsten, A. F. T. (1999) · Cerebral cortex · doi:10.1007/978-1-4615-4885-0_5 · Cited by 14
Self-citationBenn, J. J., Brown, P. M., Beckwith, L. J., Farebrother, M. J. B., & Sönksen, P. H. (1992) · Diabetes Care · doi:10.2337/diacare.15.11.1721 · Cited by 12
Saunders, J., Goméni, R., Kilborn, J., Morselli, P. L., & S�nksen, P. H. (1981) · European Journal of Clinical Pharmacology · doi:10.1007/bf00627917 · Cited by 12
Sinclair, A., Davies, I. B., & Warrington, S. (1990) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1990.tb03838.x · Cited by 1
Research works printed but not linked: 4
- Benn, 1992, Glucose turnover in type I diabetic subjects during exercise. Effect of selective and nonselective beta-blockade and insulin withdrawal, Diabetes Care, 15, 1721, 10.2337/diacare.15.11.1721 · DOI
- Lupien, 1999, Working memory is more sensitive than declarative memory to the acute effects of corticosteroids, Behavioral Neuroscience, 113, 420, 10.1037/0735-7044.113.3.420 · DOI · Paper page
- Saunders, 1981, A comparison between propranolol, practolol and betaxolol (SL75212) on the circulatory and metabolic responses to insulin-induced hypoglycaemia, European Journal of Clinical Pharmacology, 21, 177, 10.1007/BF00627917 · DOI
- Sinclair, 1990, Betaxolol and glucose-insulin relationships, British Journal of Clinical Pharmacology, 30, 699, 10.1111/j.1365-2125.1990.tb03838.x · DOI
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
Self-citationThe Neuropsychopharmacology of Fronto-Executive Function: Monoaminergic Modulation
Robbins, T. W., & Arnsten, A. F. T. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135535 · Cited by 957
Self-citationStress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752
Self-citationAdrenergic 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
Self-citationArnsten, A. F. T., Wang, M. J., & Paspalas, C. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.038 · Cited by 538
Self-citation
Metadata
- Authors
- Ramos, B. P., Colgan, L., Nou, E., Ovadia, S., Wilson, S. R., & Arnsten, A. F. T.
- Affiliations
- Yale University (US)
- Corresponding author
- Arnsten, Amy F.T.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 58
- Issue
- 11
- Pages
- 894-900
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2076484851
- Cited by
- 147
- References
- 68
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 3 · 2021: 7 · 2020: 7 · 2019: 9 · 2018: 11 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 8 · 2012: 7
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R37AG006036, R37 AG06036)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- betaxolol, beta1-adrenergic receptor, working memory, prefrontal cortex, cognitive function, noradrenergic activity, post-traumatic stress disorder, propranolol, delayed alternation, delayed response, aging
- MeSH terms
- Adrenergic beta-Antagonists, Animals, Attention, Cognition, Dose-Response Relationship, Drug, Hypnotics and Sedatives, Macaca mulatta, Male, Memory, Short-Term, Microinjections, Pancreatic Diseases, Psychomotor Performance, Stereotaxic Techniques, Betaxolol, Prefrontal Cortex, Maze Learning, Rats, Adrenergic beta-1 Receptor Antagonists
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
