Local infusion of an α-1 adrenergic agonist into the prefrontal cortex impairs spatial working memory performance in monkeys
Abstract
Background Stimulation of alpha-2 adrenoceptors in the monkey or rat prefrontal cortex (PFC) has been known to improve spatial working memory (SWM) and stimulation of alpha-1 adrenoceptors in the rat PFC has been reported to impair SWM. The present study attempted to replicate in monkey the rat experiments on alpha-1 adrenoceptor stimulation. Methods The alpha-1 adrenergic agonist phenylephrine or the alpha-2 adrenergic agonist guanfacine was infused into the dorsolateral prefrontal cortex (dlPFC) of monkeys performing the delayed-response (DR) task, a task of SWM, to see how the drugs affect SWM performance. Results Phenylephrine infusion in dlPFC significantly impaired DR performance, whereas guanfacine improved performance. The effects of both drugs were delay-dependent. Infusions outside dlPFC were ineffective. Conclusions Stimulation of prefrontal cortical alpha-1 adrenoceptors impairs SWM function in monkeys, consistent with the parallel study in rats, whereas stimulation of alpha-2 adrenoceptors improves SWM, indicating that alpha-1 and alpha-2 adrenoceptors may have opposing roles in the PFC.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These improvements are observed immediately when guanfacine is infused directly into the PFC and when administered systemically.
“These improvements are observed immediately when guanfacine is infused directly into the PFC (Mao et al., 1999) and when administered systemically (Arnsten et al., 1988; O'Neill et al., 2000; Rama et al., 1996).”
From Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders (2011) · cites this paper as Mao et al., 1999
Depletion of noradrenaline or blockade of α2A-receptors in the prefrontal cortex impairs working memory, whereas stimulation of postsynaptic α2A-receptors in the prefrontal cortex improves working memory performance.
“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 [57]
Infusion of an α1 agonist directly into the dorsolateral PFC impairs working memory performance.
“In contrast to α2A receptors, infusion of an α1 agonist directly into the dorsolateral PFC impairs working memory performance (42).”
From Catecholamine Influences on Dorsolateral Prefrontal Cortical Networks (2011) · cites this paper as [42]
Guanfacine mimics the enhancing effects of norepinephrine at postsynaptic α2A-receptors in the PFC, strengthening network connectivity.
“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 [42]
Stimulation of postsynaptic α2A receptors in dorsolateral PFC improves working memory performance.
“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 [42]
Direct infusions of guanfacine into lateral PFC improved working memory and associative learning in monkeys.
“For example, direct infusions of guanfacine into the lateral PFC improved performance of working memory and associative learning tasks in monkeys (Mao et al., 1999, Wang et al., 2004).”
From Guanfacine’s mechanism of action in treating prefrontal cortical disorders: Successful translation across species (2020) · cites this paper as Mao et al., 1999
Cites
Circuitry of Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory
Goldman‐Rakic, P. S. (1987) · Comprehensive Physiology · doi:10.1002/cphy.cp010509 · Cited by 1,960 · see citing works
Arnsten, A. F. T., & Goldman-Rakic, P. S. (1985) · Science · doi:10.1126/science.2999977 · Cited by 549 · see citing works
Self-citationArnsten, A. F. T. (1998) · Science · doi:10.1126/science.280.5370.1711 · Cited by 341 · see citing works
Self-citationLi, B.-M., & Mei, Z.-T. (1994) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(05)80034-2 · Cited by 186 · see citing works
Self-citationCai, J. X., Ma, Y.-Y., Xu, L., & Hu, X.-T. (1993) · Brain Research · doi:10.1016/0006-8993(93)91034-p · Cited by 122 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Self-citationBerridge, C. W., & Waterhouse, B. D. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00143-7 · Cited by 2,529 · see citing works
Neurobiology of Executive Functions: Catecholamine Influences on Prefrontal Cortical Functions
Arnsten, A. F. T., & Li, B.-M. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.08.019 · Cited by 948 · see citing works
Self-citationStress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval
Roozendaal, B. (2002) · Neurobiology of Learning and Memory · doi:10.1006/nlme.2002.4080 · Cited by 838 · see citing works
Wang, M., Ramos, B. P., Paspalas, C. D., Shu, Y., Simen, A., Duque, A., Vijayraghavan, S., Brennan, A., Dudley, A., Nou, E., et al. (2007) · Cell · doi:10.1016/j.cell.2007.03.015 · Cited by 672 · see citing works
Self-citationScahill, L., Chappell, P. B., Kim, Y. S., Schultz, R. T., Katsovich, L., Shepherd, E., Arnsten, A. F. T., Cohen, D. J., & Leckman, J. F. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.7.1067 · Cited by 588 · see citing works
Self-citationArnsten, A. F. T., Wang, M. J., & Paspalas, C. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.038 · Cited by 538 · see citing works
Self-citationCatecholamine Influences on Dorsolateral Prefrontal Cortical Networks
Arnsten, A. F. T. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.027 · Cited by 493 · see citing works
Self-citationStimulants: Therapeutic Actions in ADHD
Arnsten, A. F. T. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301164 · Cited by 473 · see citing works
Self-citationArnsten, A. F. T., & Pliszka, S. R. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.01.020 · Cited by 383 · see citing works
Self-citationPrefrontal Serotonin Depletion Affects Reversal Learning But Not Attentional Set Shifting
Clarke, H. F., Walker, S. C., Crofts, H. S., Dalley, J. W., Robbins, T. W., & Roberts, A. C. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3690-04.2005 · Cited by 358 · see citing works
Arnsten, A. F., & Dudley, A. G. (2005) · Behavioral and Brain Functions · doi:10.1186/1744-9081-1-2 · Cited by 363 · see citing works
Self-citationThiele, A., & Bellgrove, M. A. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.008 · Cited by 350 · see citing works
Protein kinase C overactivity impairs prefrontal cortical regulation of working memory
Birnbaum, S. G., Yuan, P. X., Wang, M., Vijayraghavan, S., Bloom, A. K., Davis, D. J., Gobeske, K. T., Sweatt, J. D., Manji, H. K., & Arnsten, A. F. T. (2004) · Science · doi:10.1126/science.1100021 · Cited by 318 · see citing works
Self-citationBirnbaum, S., Gobeske, K. T., Auerbach, J., Taylor, J. R., & Arnsten, A. F. T. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00138-9 · Cited by 281 · see citing works
Self-citationModulators in concert for cognition: Modulator interactions in the prefrontal cortex
Briand, L. A., Gritton, H., Howe, W. M., Young, D. A., & Sarter, M. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.06.007 · Cited by 216 · see citing works
ADHD and the Prefrontal Cortex
Arnsten, A. F. T. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2009.01.018 · Cited by 220 · see citing works
Self-citationBondi, C. O., Jett, J. D., & Morilak, D. A. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.04.016 · Cited by 88 · see citing works
Arnsten, A. F. T. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107327 · Cited by 75 · see citing works
Self-citationArnsten, A. F. T., & Wang, M. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103617 · Cited by 50 · see citing works
Self-citationNoradrenergic α1-Adrenoceptor Actions in the Primate Dorsolateral Prefrontal Cortex
Datta, D., Yang, S.-T., Galvin, V. C., Solder, J., Luo, F., Morozov, Y. M., Arellano, J., Duque, A., Rakic, P., Arnsten, A. F. T., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.2472-18.2019 · Cited by 44 · see citing works
Self-citationRole of KCNQ potassium channels in stress-induced deficit of working memory
Arnsten, A. F. T., Jin, L. E., Gamo, N. J., Ramos, B., Paspalas, C. D., Morozov, Y. M., Kata, A., Bamford, N. S., Yeckel, M. F., Kaczmarek, L. K., et al. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100187 · Cited by 27 · see citing works
Self-citation
- Authors
- Mao, Z.-M., Arnsten, A. F. T., & Li, B.-M.
- Affiliations
- Yale University (US)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Li, Bao-Ming
- ORCID
- Arnsten, Amy F.T
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 46
- Issue
- 9
- Pages
- 1259-1265
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2053217435
- Cited by
- 156
- References
- 5
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 5 · 2015: 8 · 2014: 13 · 2013: 4 · 2012: 8
- FWCI
- 1.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (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 › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- alpha1-adrenoceptors, alpha2-adrenoceptors, prefrontal cortex, spatial working memory, phenylephrine, guanfacine, dorsolateral prefrontal cortex, delayed response task, monkeys
- MeSH terms
- Adrenergic alpha-Agonists, Animals, Female, Infusions, Parenteral, Macaca mulatta, Male, Memory, Short-Term, Norepinephrine, Phenylephrine, Spatial Behavior, Guanfacine, Prefrontal Cortex, Adrenergic alpha-1 Receptor Agonists, Adrenergic alpha-2 Receptor Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
