The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Reserpine impairs spatial working memory performance in monkeys: reversal by the α2-adrenergic agonist clonidine
Abstract
Repeated daily treatment with the catecholamine-depleting agent, reserpine, dramatically reduced performance on the delayed response task, a test of spatial working memory that depends upon the integrity of the prefrontal cortex. Delayed response performance fell from an average of 27.2/30 trials correct before reserpine treatment to an average of 20.4/30 trials correct after repeated reserpine administration. Injection of the alpha 2-adrenergic agonist, clonidine (0.0001-0.05 mg/kg), to chronic reserpine-treated monkeys significantly restored performance on the delayed response task; performance after an optimal dose averaged 27.8/30 trials correct. Clonidine's beneficial effects on delayed response performance were longlasting; monkeys remained improved for more than 24 h after a single clonidine injection. The finding that clonidine is efficacious in reserpinized animals supports the hypothesis that alpha 2-adrenergic agonists improve cognitive function through actions at postsynaptic, alpha 2-adrenergic receptors on non-adrenergic cells. In contrast to the delayed response task, reserpine had little effect on performance of a visual discrimination task, a reference memory task which does not depend on the prefrontal cortex. These results emphasize the importance of postsynaptic, alpha 2-adrenergic mechanisms in the regulation of working memory.
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“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 Cai et al., 1993
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 [56]
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 [41]
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 [41]
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 Cai et al., 1993
Citations
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Methylphenidate does not enhance visual working memory but benefits motivation in macaque monkeys
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Metadata
- Authors
- Cai, J. X., Ma, Y.-Y., Xu, L., & Hu, X.-T.
- Affiliations
- Kunming Institute of Zoology (CN)
- Corresponding author
- Jing Xia Cai
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1993-06
- Volume
- 614
- Issue
- 1-2
- Pages
- 191-196
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1970116189
- Cited by
- 122
- References
- 16
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 7 · 2015: 5 · 2014: 1 · 2013: 1 · 2012: 4
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- 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
- reserpine, clonidine, spatial working memory, alpha2-adrenoceptors, prefrontal cortex, delayed response task, reference memory, visual discrimination, catecholamine depletion, cognitive enhancement, monkeys
- MeSH terms
- Adrenergic alpha-Agonists, Animals, Blood Pressure, Clonidine, Cognition, Discrimination, Psychological, Female, Hypnotics and Sedatives, Macaca mulatta, Male, Memory, Short-Term, Synaptic Transmission, Norepinephrine, Reserpine, Reversal Learning, Space Perception
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