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.
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“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]
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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
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