Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys
Abstract
Dopamine (DA) D1 receptor compounds were examined in monkeys for effects on the working memory functions of the prefrontal cortex and on the fine motor abilities of the primary motor cortex. The D1 antagonist, SCH23390, the partial D1 agonist, SKF38393, and the full D1 agonist, dihydrexidine, were characterized in young control monkeys, and in aged monkeys with naturally occurring catecholamine depletion. In addition, SKF38393 was tested in young monkeys experimentally depleted of catecholamines with chronic reserpine treatment. Injections of SCH23390 significantly impaired the memory performance of young control monkeys, but did not impair aged monkeys with presumed catecholamine depletion. Conversely, the partial agonist, SKF38393, improved the depleted monkeys (aged or reserpine-treated) but did not improve young control animals. The full agonist, dihydrexidine, did improve memory performance in young control monkeys as well as in a subset of aged monkeys. Consistent with D1 receptor mechanisms, agonist-induced improvements were blocked by SCH23390. Drug effects on memory performance occurred independently of effects on fine motor performance. These results underscore the importance of DA D1 mechanisms in cognitive function, and provide functional evidence of DA system degeneration in aged monkeys. Finally, high doses of D1 agonists impaired memory performance in aged monkeys, suggesting that excessive D1 stimulation may be deleterious to cognitive function.
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An intermediate (optimal) level of dopaminergic D1 receptor activation is important for working memory tasks to be accomplished.
“The common finding among these studies is the importance of an intermediate, that is, optimal, level of dopaminergic (D1) receptor activation to enable working memory tasks to be accomplished.”
From The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes-Dodson Law (2007) · cites this paper as Arnsten et al. [414]
There is an inverted-U-shaped relationship between dopamine receptor signaling in the prefrontal cortex and working memory performance.
“A number of researchers have commented on the inverted-U-shaped relationship between dopamine receptor signaling in the prefrontal cortex and working memory performance (Arnsten et al. [414]; Murphy et al. [415]; Cai and Arnsten [416]; Arnsten [363]; Arnsten [417]; Brunel and Wang [418]; Dreher et al. [419]; Yamashita and Tanaka [420]; Williams and Castner [421]; Tanaka et al. [422]).”
From The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes-Dodson Law (2007) · cites this paper as Arnsten et al. [414]
Cognitive control deficits are often associated with alterations in dopamine transmission in prefrontal cortex and striatum.
“Cognitive control deficits are often associated with alterations in dopamine transmission in prefrontal cortex and striatum (Arnsten et al., 1994; Cai and Arnsten, 1997; Cools, 2008; Cools and D'Esposito, 2011; Landau et al., 2009; Vernaleken et al., 2007)”
From Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity (2014) · cites this paper as Arnsten et al., 1994
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“Animal studies reported that the WM effect of dopaminergic agents (e.g., dihydrexidine or other D1 agonists) depends on the baseline dopamine level (Arnsten et al., 1994; Cai & Arnsten, 1997).”
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- Authors
- Arnsten, A. F. T., Cai, J. X., Murphy, B. L., & Goldman-Rakic, P. S.
- Affiliations
- Yale University (US)
- Kunming Institute of Zoology (CN)
- Venue
- Psychopharmacology
- Published
- 1994-10
- Volume
- 116
- Issue
- 2
- Pages
- 143-151
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2061833498
- Cited by
- 566
- References
- 30
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 8 · 2023: 18 · 2022: 15 · 2021: 9 · 2020: 7 · 2019: 14 · 2018: 17 · 2017: 11 · 2016: 16 · 2015: 25 · 2014: 27 · 2013: 20 · 2012: 20
- FWCI
- 4.65
- 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)
- National Institute of Mental Health (MH 44866, P50MH044866)
- 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 › Schizophrenia research and treatment
- Keywords
- dopamine D1 receptor, working memory, prefrontal cortex, primary motor cortex, fine motor performance, aging, catecholamine depletion, reserpine, SCH 23390, SKF 38393, dihydrexidine, cognitive function
- MeSH terms
- Aging, Animals, Behavior, Animal, Benzazepines, Cognition, Female, Macaca mulatta, Phenanthridines, Psychomotor Performance, Reserpine, 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine, Prefrontal Cortex, Receptors, Dopamine D1
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