The alpha-1 adrenergic agonist, cirazoline, impairs spatial working memory performance in aged monkeys
Open accessAbstract
The alpha-1 adrenergic agonist, cirazoline, was examined for effects on spatial working memory performance in aged rhesus monkeys. Cirazoline has additional high affinity for imidazoline receptors and has good brain penetrance when administered systemically. Spatial working memory was assessed using the variable delayed response task, a test dependent upon prefrontal cortical function in monkeys. Low doses of cirazoline (0.00001-0.001 mg/kg) impaired delayed response performance significantly. This impairment did not appear to result from nonspecific changes in behavior, because cirazoline had no significant effect on performance of control trials where the delay was "0" s, and had no significant effect on behavioral ratings. Impairment was reversed by pretreatment with the alpha-1 adrenergic antagonist, prazosin, consistent with drug actions at alpha-1 adrenergic receptors. In contrast, preliminary data suggest that higher cirazoline doses (0.001-0.01 mg/kg) occasionally produced improved performance that was not reversed by prazosin, but rather, by the imidazoline/alpha-2 adrenergic antagonist, idazoxan. The finding that alpha-1 adrenergic receptor stimulation impairs spatial working memory performance complements previous research demonstrating that alpha-2 adrenergic receptor stimulation improves working memory, and suggests that norepinephrine may have opposing actions at alpha-1 vs. alpha-2 receptors in the prefrontal cortex as it does in the hypothalamus and thalamus.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Systemic administration of an α1 agonist that crosses the blood brain barrier impairs working memory performance, while administration of an α1 antagonist, e.g., prazosin, can protect working memory performance during stress.
“Systemic administration of an α1 agonist that crosses the blood brain barrier also impairs working memory performance, while administration of an α1 antagonist, e.g., prazosin, can protect working memory performance during stress (37,50,51).”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [50]
The Drug Administration and Results sections report systemic cirazoline treatment in aged monkeys, impaired spatial working memory, and reversal of that impairment by prazosin (page numbers unavailable). The Discussion proposes that α1 mechanisms may contribute to cognitive impairment during stress, but the paper does not show that prazosin protects working memory during stress. It describes cirazoline's brain penetrance as purported rather than directly demonstrating it. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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 · see citing works
Arnsten, A. F. T., & Goldman-Rakic, P. S. (1985) · Science · doi:10.1126/science.2999977 · Cited by 549 · see citing works
Self-citationLi, B.-M., & Mei, Z.-T. (1994) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(05)80034-2 · Cited by 186 · see citing works
Cai, J. X., Ma, Y.-Y., Xu, L., & Hu, X.-T. (1993) · Brain Research · doi:10.1016/0006-8993(93)91034-p · Cited by 122 · see citing works
Flagged first, then by citations
Research works printed but not linked: 4
- Arnsten, A. F. T.; Lin, C. H.; van Dyck, C. H.; Stanhope, K. J.: The effects of 5-HT3 receptor antagonists on cognitive perfor- mance in aged monkeys. Neurobiol. Aging; 18:21-28; 1997.
- Lapin, B. A.; Krilova, R. I.; Cherkovich, G. M.; Asanov, N. S.: Observations from Sukhumi. In: Bowden, D. M., ed. Aging in nonhuman primates. New York: van Nostrand Reinhold Co.; 1979:14-37.
- Murphy, B. L.; Arnsten, A. F. T.; Goldman-Rakic, P. S.; Roth, R. H.: Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and mon- keys. Proc. Natl. Acad. Sci. USA 93:1325-1329; 1996.
- Murphy, B. L.; Arnsten, A. F. T.; Jentsch, J. D.; Roth, R. H.: (+)HA966 and clonidine prevent FG7142-induced increases in prefrontal cortical dopamine turnover and block FG7142- induced impairments in spatial working memory in rats and mon- keys. J. Neurosci.; 16:7768-7775; 1996.
Cited by
Sorted by citations
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-citationRoozendaal, B., & McGaugh, J. L. (2011) · Behavioral Neuroscience · doi:10.1037/a0026187 · Cited by 445 · see citing works
Arnsten, A. F. T. (1998) · Science · doi:10.1126/science.280.5370.1711 · Cited by 341 · see citing works
Self-citationProtein kinase C overactivity impairs prefrontal cortical regulation of working memory
Birnbaum, S. G., Yuan, P. X., Wang, M., Vijayraghavan, S., Bloom, A. K., Davis, D. J., Gobeske, K. T., Sweatt, J. D., Manji, H. K., & Arnsten, A. F. T. (2004) · Science · doi:10.1126/science.1100021 · Cited by 318 · see citing works
Self-citationBirnbaum, 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 · see citing works
Self-citationNoradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex
Datta, D., Yang, S.-T., Galvin, V. C., Solder, J., Luo, F., Morozov, Y. M., Arellano, J., Duque, A., Rakic, P., Arnsten, A. F. T., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.2472-18.2019 · Cited by 44 · see citing works
Self-citation
- Authors
- Arnsten, A. F. T., & Jentsch, J. D.
- Affiliations
- Yale University (US)
- Corresponding author
- Arnsten, A.F.T.
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 1997-09
- Volume
- 58
- Issue
- 1
- Pages
- 55-59
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2118090572
- Cited by
- 85
- References
- 4
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 1 · 2014: 6 · 2013: 2 · 2012: 4
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmacology Biochemistry and Behavior (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG06036)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cirazoline, alpha1-adrenoceptors, spatial working memory, aging, rhesus monkeys, prazosin, idazoxan, imidazoline receptors, alpha2-adrenoceptors, norepinephrine, prefrontal cortex, cognitive impairment
- MeSH terms
- Adrenergic alpha-Agonists, Aging, Animals, Cognition, Depression, Chemical, Dose-Response Relationship, Drug, Female, Imidazoles, Macaca mulatta, Memory, Short-Term, Space Perception, Idazoxan, Adrenergic alpha-1 Receptor Agonists, Adrenergic alpha-2 Receptor Agonists
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
