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Delayed-response deficit induced by local injection of the α2-adrenergic antagonist yohimbine into the dorsolateral prefrontal cortex in young adult monkeys
Abstract
Two young adult monkeys (Macaca mullata) were trained to perform a delayed-response task that required the monkeys to remember a cued spatial position (left or right) over a delay interval and then to make a response to the cued position. Local injection of the alpha 2-adrenergic antagonist yohimbine (10 micrograms in 2 microliters saline) into the dorsolateral prefrontal cortex (Walker's area 46 and area 9) impaired the performance of the delayed-response task, and it was without effect on the performance of the task if there was no delay between the cue and choice signals. The main performing error after injection of yohimbine was that the monkeys responded to uncued position with higher rate. Local injection of the alpha 1-adrenergic antagonist prazosin (10 microgram in 2 microliters saline) or the beta-adrenergic antagonist propranolol (10 micrograms in 2 microliters saline) into the same cortical areas induced no significant effect on the performance of the task. The present study suggests that prefrontal alpha 2-adrenoceptors play an important role in the spatial working memory in young adult monkeys.
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In the citing paper
“Studies in animals indicate that NE engages predominantly α2-receptors in the PFC when the subject is alert and interested (Li and Mei, 1994), while actions at α1-receptors and possibly β-receptors are predominant under stressful conditions (Birnbaum et al., 2004; Ramos et al., 2005).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Li and Mei, 1994
In the citing paper
“Blockade of α2A-receptors in the monkey PFC with local yohimbine infusions markedly impairs PFC regulation of attention and behavior, inducing poor impulse control and locomotor hyperactivity (Li and Mei, 1994; Ma et al., 2005; Ma et al., 2003).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Li and Mei, 1994
In the citing paper
“Conversely, yohimbine blockade of α2-receptors in the PFC recreates the symptoms of ADHD: inducing locomotor hyperactivity (Ma et al., 2005), poor impulse control (Ma et al., 2003), and weaker working memory (Li and Mei, 1994).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Li and Mei, 1994
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 [53]
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 [53]
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 [36]
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 [36]
In the citing paper
“Conversely, infusion of the α2-AR antagonist, yohimbine, into the monkey dlPFC impaired working memory (Li & Mei, 1994), impulse control (Ma, Qi, Peng, & Li, 2003) and regulation of locomotor activity (Ma, Arnsten, & Li, 2005), producing an “ADHD-like” phenotype.”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Li & Mei, 1994
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Arnsten, A. F. T. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1274-9 · Cited by 32
Abdallah, C. G., Averill, L. A., Krystal, J. H., Southwick, S. M., & Arnsten, A. F. T. (2016) · Behavioral and Brain Sciences · doi:10.1017/s0140525x15001727 · Cited by 30
Computational Modeling of Catecholamines Dysfunction in Alzheimer’s Disease at Pre-Plaque Stage
Caligiore, D., Silvetti, M., D’Amelio, M., Puglisi‐Allegra, S., & Baldassarre, G. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200276 · Cited by 30
Metadata
- Authors
- Li, B.-M., & Mei, Z.-T.
- Affiliations
- Chinese Academy of Sciences (CN)
- ORCID
- Li, Bao-Ming
- Venue
- Behavioral and Neural Biology
- Publisher
- Elsevier BV
- Published
- 1994-09
- Volume
- 62
- Issue
- 2
- Pages
- 134-139
- ISSN
- 0163-1047 (ISSN-L)
- OpenAlex
- W2075473160
- Cited by
- 186
- References
- 15
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 4 · 2018: 7 · 2017: 4 · 2016: 9 · 2015: 13 · 2014: 7 · 2013: 13 · 2012: 8
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioral and Neural Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- yohimbine, alpha2-adrenoceptors, dorsolateral prefrontal cortex, delayed response task, spatial working memory, prazosin, propranolol, alpha-blockers, beta-blockers
- MeSH terms
- Animals, Brain Mapping, Female, Macaca mulatta, Orientation, Prazosin, Propranolol, Psychomotor Performance, Reaction Time, Mental Recall, Yohimbine, Prefrontal Cortex, Receptors, Adrenergic, alpha-1, Receptors, Adrenergic, alpha-2
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