CoChat
Sign Up
Cited by 149Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesNeuroscience and Neuropharmacology Research

The beta-1 adrenergic antagonist, betaxolol, improves working memory performance in rats and monkeys

Ramos, Brian P., Colgan, Lesley, Nou, Eric, Ovadia, Shira, Wilson, Steven R., Arnsten, Amy F.T.·2005·Biological Psychiatry
DOI 10.1016/j.biopsych.2005.05.022
Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1016/j.biopsych.2005.05.022

Cites

66 of 66 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • Studies in animals indicate that norepinephrine engages predominantly α2-receptors in the PFC when the subject is alert and interested, while actions at α1-receptors and possibly β-receptors are predominant under stressful conditions.

    “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

  • 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 [55]

  • 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 [38]

  • Norepinephrine may also drive cAMP signaling via the β1-AR, although this pathway requires further study.

    “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]

Cites

Flagged first, then by citations

2 of the 68 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

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.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2005-12
Volume
58
Issue
11
Pages
894-900
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2005.05.022
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
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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