The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
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.
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In the citing paper
“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
In the citing paper
“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]
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 [52]
In the citing paper
“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]
In the citing paper
“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]
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 [35]
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
Citations
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Cited by
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Stress signalling pathways that impair prefrontal cortex structure and function
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Metadata
- 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
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