Role of adenosine A2A receptors in hot and cold cognition: effects of single-dose istradefylline in healthy volunteers
Role of adenosine A2A receptors in hot and cold cognition: effects of single-dose istradefylline in healthy volunteers
The role of the adenosine neurochemical system in human cognition is under-studied, despite such receptors being distributed throughout the brain. The aim of this study was to shed light on the role of the adenosine A2A receptors in human cognition using single-dose istradefylline. Twenty healthy male participants, aged 19–49, received 20 mg istradefylline and placebo, in a randomized, double-blind, placebo-controlled cross-over design. Cognition was assessed using computerized cognitive tests, covering both cold (non-emotional) and hot (emotion-laden) domains. Cardiovascular data were recorded serially. Cognitive effects of istradefylline were explored using repeated measures analysis of variance and paired t-tests as appropriate. On the EMOTICOM battery, there was a significant effect of istradefylline versus placebo on the Social Information Preference task (t = 2.50, p = 0.02, d=-0.59), indicating that subjects on istradefylline interpreted social situations more positively. No other significant effects were observed on other cognitive tasks, nor in terms of cardiovascular measures (pulse and blood pressure). De-briefing indicated that blinding was successful, both for participants and the research team. Further exploration of the role of adenosine A2A receptors in emotional processing may be valuable, given that abnormalities in related cognitive functions are implicated in neuropsychiatric disorders. The role of adenosine systems in human cognition requires further clarification, including with different doses of istradefylline and over different schedules of administration.
Adenosine, Cognition, Istradefylline
55-64
Hook, Roxanne
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Masanori, Isobe1
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Savulich, George
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Grant, Jon E.
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Ioannidis, Konstantinos
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Christmas, David
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Sahakian, Barbara J.
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Robbins, Trevor W.
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Chamberlain, Samuel
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June 2023
Hook, Roxanne
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Masanori, Isobe1
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Savulich, George
abded076-0950-403f-951a-0fe4cf67477a
Grant, Jon E.
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Ioannidis, Konstantinos
0dfc1d89-41be-4d02-ae50-698117e80141
Christmas, David
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Sahakian, Barbara J.
e689cd5c-b84f-4503-86ca-7526cf340121
Robbins, Trevor W.
20dd57dd-dbf3-4aaa-b7ba-bb4387ffcbc7
Chamberlain, Samuel
8a0e09e6-f51f-4039-9287-88debe8d8b6f
Hook, Roxanne, Masanori, Isobe1, Savulich, George, Grant, Jon E., Ioannidis, Konstantinos, Christmas, David, Sahakian, Barbara J., Robbins, Trevor W. and Chamberlain, Samuel
(2023)
Role of adenosine A2A receptors in hot and cold cognition: effects of single-dose istradefylline in healthy volunteers.
Comprehensive Psychiatry, 71, .
(doi:10.1016/j.euroneuro.2023.03.006).
Abstract
The role of the adenosine neurochemical system in human cognition is under-studied, despite such receptors being distributed throughout the brain. The aim of this study was to shed light on the role of the adenosine A2A receptors in human cognition using single-dose istradefylline. Twenty healthy male participants, aged 19–49, received 20 mg istradefylline and placebo, in a randomized, double-blind, placebo-controlled cross-over design. Cognition was assessed using computerized cognitive tests, covering both cold (non-emotional) and hot (emotion-laden) domains. Cardiovascular data were recorded serially. Cognitive effects of istradefylline were explored using repeated measures analysis of variance and paired t-tests as appropriate. On the EMOTICOM battery, there was a significant effect of istradefylline versus placebo on the Social Information Preference task (t = 2.50, p = 0.02, d=-0.59), indicating that subjects on istradefylline interpreted social situations more positively. No other significant effects were observed on other cognitive tasks, nor in terms of cardiovascular measures (pulse and blood pressure). De-briefing indicated that blinding was successful, both for participants and the research team. Further exploration of the role of adenosine A2A receptors in emotional processing may be valuable, given that abnormalities in related cognitive functions are implicated in neuropsychiatric disorders. The role of adenosine systems in human cognition requires further clarification, including with different doses of istradefylline and over different schedules of administration.
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Submitted date: 4 July 2022
Accepted/In Press date: 7 March 2023
e-pub ahead of print date: 27 March 2023
Published date: June 2023
Additional Information:
Funding Information:
This research was funded by a Wellcome Trust Clinical Fellowship to Dr Chamberlain (Reference: 110049/Z/15/Z). Dr Chamberlain receives honoraria from Elsevier for editorial work at Comprehensive Psychiatry, and at Neuroscience & Biobehavioral Reviews. Dr Sahakian consults for Cambridge Cognition, Greenfield BioVentures and Cassava Sciences. Dr Sahakian's research is funded by Eton College and the Wallitt Foundation and is conducted within the NIHR MedTech and in vitro diagnostic Co-operative (MIC) and the NIHR Cambridge Biomedical Research Centre (BRC) Mental Health Theme. Dr Robbins consults for Cambridge Cognition, and has received research grants from GSK, Shionogi Royalties, Cambridge Cognition (CANTAB); Editorial Honoraria: Springer Nature; Elsevier. Dr. Grant has research grants from Otsuka and Biohaven Pharmaceuticals and receives a yearly stipend from Springer Publishing for acting as editor in chief of the Journal of Gambling Studies. The other authors report no relevant disclosures. This research was funded in whole, or in part, by Wellcome [Grant number 110049/Z/15/Z and 110049/Z/15/A]. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. The authors would like to thank the anonymous peer reviewers for their detailed comments and advice.
Funding Information:
This research was funded by a Wellcome Trust Clinical Fellowship to Dr Chamberlain (Reference: 110049/Z/15/Z). Dr Chamberlain receives honoraria from Elsevier for editorial work at Comprehensive Psychiatry, and at Neuroscience & Biobehavioral Reviews. Dr Sahakian consults for Cambridge Cognition, Greenfield BioVentures and Cassava Sciences. Dr Sahakian's research is funded by Eton College and the Wallitt Foundation and is conducted within the NIHR MedTech and in vitro diagnostic Co-operative (MIC) and the NIHR Cambridge Biomedical Research Centre (BRC) Mental Health Theme. Dr Robbins consults for Cambridge Cognition, and has received research grants from GSK, Shionogi Royalties, Cambridge Cognition (CANTAB); Editorial Honoraria: Springer Nature; Elsevier. Dr. Grant has research grants from Otsuka and Biohaven Pharmaceuticals and receives a yearly stipend from Springer Publishing for acting as editor in chief of the Journal of Gambling Studies. The other authors report no relevant disclosures. This research was funded in whole, or in part, by Wellcome [Grant number 110049/Z/15/Z and 110049/Z/15/A ]. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
© 2023
Keywords:
Adenosine, Cognition, Istradefylline
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Local EPrints ID: 468335
URI: http://eprints.soton.ac.uk/id/eprint/468335
ISSN: 0010-440X
PURE UUID: c824517c-ab0a-4150-96d4-503c0c759b5d
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Date deposited: 10 Aug 2022 18:11
Last modified: 30 Aug 2024 04:01
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Contributors
Author:
Roxanne Hook
Author:
Isobe1 Masanori
Author:
George Savulich
Author:
Jon E. Grant
Author:
Konstantinos Ioannidis
Author:
David Christmas
Author:
Barbara J. Sahakian
Author:
Trevor W. Robbins
Author:
Samuel Chamberlain
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