The Contribution of α2-Noradrenergic Mechanisms to Prefrontal Cortical Cognitive Function: Potential Significance for Attention-Deficit Hyperactivity Disorder
Abstract
This article aims to review research in nonhuman primates demonstrating that norepinephrine can enhance the cognitive functioning of the prefrontal cortex through actions at alpha 2 A-adrenergic receptors postjunctional to noradrenergic terminals. As prefrontal cortex cognitive deficits are prominent in several psychiatric disorders, including attention-deficit hyperactivity disorder, these basic findings may have relevance for the development of novel pharmacotherapies.
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Development of guanfacine's use in ADHD was based on understanding its prefrontal enhancement in monkeys and recognition that ADHD is a PFC disorder.
“with the development of guanfacine’s use in ADHD based on understanding its prefrontal enhancement in monkeys (Arnsten and Contant, 1992, Arnsten et al., 1996), and the recognition that ADHD is a PFC disorder.”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Arnsten et al., 1996
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- Authors
- Arnsten, A. F. T.
- Affiliations
- Yale University (US)
- Corresponding author
- Arnsten, Amy F.T.
- ORCID
- Arnsten, Amy F.T.
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 1996-05-01
- Volume
- 53
- Issue
- 5
- Pages
- 448
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2042348492
- Cited by
- 458
- References
- 14
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 10 · 2016: 23 · 2015: 13 · 2014: 18 · 2013: 11 · 2012: 21
- FWCI
- 8.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- 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
- alpha2A-adrenergic receptor, norepinephrine, prefrontal cortex, cognitive function, noradrenergic terminals, postjunctional receptors, attention deficit hyperactivity disorder, mental illness, pharmacotherapy
- MeSH terms
- Adrenergic alpha-Agonists, Animals, Haplorhini, Attention Deficit Disorder with Hyperactivity, Clonidine, Cognition Disorders, Humans, Locus Coeruleus, Models, Neurological, Neural Pathways, Norepinephrine, Guanfacine, Prefrontal Cortex, Receptors, Adrenergic, alpha-2
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