Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task
Abstract
With advancing age, monkeys become impaired on a test of spatial working memory, the delayed response task, and show increased susceptibility to interference from irrelevant stimuli (Bartus and Dean 1979). Alpha-2 adrenergic agonists such as clonidine and guanfacine have been shown to improve the delayed response performance of aged monkeys under standard testing conditions (e.g. Arnsten et al. 1988). The current study examined whether these drugs could protect the delayed response performance of aged monkeys when irrelevant stimuli were presented during the delay intervals. Aged monkeys were tested on the variable delayed response task with short delays to minimize memory demands and optimize performance on control (no interference) sessions. During interference sessions, distractors were presented during the delays on 9 of the 30 trials ("distractor" trials). If the aged monkeys had been pretreated with saline, performance was significantly disrupted by the irrelevant stimuli compared to matched saline control sessions. This impairment was not only evident on the 9 distractor trials, but on the 21 remaining "nondistractor" trials as well. However, if the aged monkeys had been pretreated with clonidine or guanfacine, performance was not impaired on the interference sessions. This beneficial effect of the alpha-2 agonists was most apparent on the nondistractor trials. Guanfacine was able to decrease the harmful effects of distraction without any apparent sedative side effects…
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Guanfacine enhances various PFC functions in animals, including improvements in working memory, behavioral inhibition, and reduced distractibility.
“Guanfacine enhances various PFC functions in animals, including improvements in working memory (Arnsten et al., 1988), behavioral inhibition (Steere and Arnsten, 1997), and reduced distractibility (Arnsten and Contant, 1992).”
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 Contant, 1992
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 and Contant, 1992
Guanfacine reduces disruption by distractors in aged monkeys.
“reduces disruption by distractors (Fig. 7C; (Arnsten and Contant, 1992, O'Neill et al., 2000))”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Arnsten and Contant, 1992
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References 54 · Cited by 168
- Authors
- Arnsten, A. F. T., & Contant, T. A.
- Affiliations
- Yale University (US)
- ORCID
- Arnsten, A. F. T.
- Venue
- Psychopharmacology
- Published
- 1992-07
- Volume
- 108
- Issue
- 1-2
- Pages
- 159-169
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2067197183
- Cited by
- 168
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 6 · 2015: 4 · 2014: 2 · 2013: 3 · 2012: 3
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (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
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- alpha-2 adrenergic agonists, clonidine, guanfacine, aging, delayed response task, distractibility, distractor interference, spatial working memory, idazoxan, alpha2-adrenoceptors, aged monkeys, cognitive aging
- MeSH terms
- Adrenergic alpha-Agonists, Adrenergic alpha-Antagonists, Aging, Animals, Attention, Benzazepines, Clonidine, Cognition, Conditioning, Operant, Dioxanes, Female, Macaca mulatta, Memory, Psychomotor Performance, Idazoxan
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