Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task

Angharad de Cates; Lucy C. Wright; Marieke A.G. Martens; Daisy Gibson; Cagdas Türkmen; Nicola Filippini; Philip J. Cowen; Catherine J. Harmer; Susannah E. Murphy

doi:10.1038/s41398-021-01568-4

Déjà-vu? Neural and behavioural effects of the 5-HT₄ receptor agonist, prucalopride, in a hippocampal-dependent memory task

Angharad de Cates^*, Lucy C. Wright, Marieke A.G. Martens, Daisy Gibson, Cagdas Türkmen, Nicola Filippini, Philip J. Cowen, Catherine J. Harmer, Susannah E. Murphy

^*Corresponding author for this work

Applied Health Sciences

Research output: Contribution to journal › Article › peer-review

31 Downloads (Pure)

Abstract

Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT₄ receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT₄ receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT₄ partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT₄-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.

Original language	English
Article number	497
Number of pages	9
Journal	Translational Psychiatry
Volume	11
DOIs	https://doi.org/10.1038/s41398-021-01568-4
Publication status	Published - 4 Oct 2021

Bibliographical note

Funding:
ANdeC is funded by a Wellcome Trust Clinical Doctoral Research Fellowship (216430/Z/19/Z), and has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation. MM is and NF was at the time of the study funded by the NIHR Oxford Health Biomedical Research Centre. This research was supported by the NIHR Oxford Health Biomedical Research Centre and by the Wellcome Centre for Integrative Neuroscience (WIN) (203139/Z/16/Z). The views expressed are those of the authors and not necessarily those of Wellcome, the NHS, the NIHR, or the Department of Health. None of these bodies had a significant role in the design, collection and analysis of data, or decision to publish this article. This research was funded in whole, or in part, by the Wellcome Trust. For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission.

Access to Document

10.1038/s41398-021-01568-4Licence: Creative Commons: Attribution (CC BY)

deCatesA2021DéjàFinal published version, 1.18 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

@article{c19234def6f94aa6aed5a5e473223ee4,

title = "D{\'e}j{\`a}-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task",

abstract = "Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT4 partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.",

author = "{de Cates}, Angharad and Wright, {Lucy C.} and Martens, {Marieke A.G.} and Daisy Gibson and Cagdas T{\"u}rkmen and Nicola Filippini and Cowen, {Philip J.} and Harmer, {Catherine J.} and Murphy, {Susannah E.}",

note = "Funding: ANdeC is funded by a Wellcome Trust Clinical Doctoral Research Fellowship (216430/Z/19/Z), and has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation. MM is and NF was at the time of the study funded by the NIHR Oxford Health Biomedical Research Centre. This research was supported by the NIHR Oxford Health Biomedical Research Centre and by the Wellcome Centre for Integrative Neuroscience (WIN) (203139/Z/16/Z). The views expressed are those of the authors and not necessarily those of Wellcome, the NHS, the NIHR, or the Department of Health. None of these bodies had a significant role in the design, collection and analysis of data, or decision to publish this article. This research was funded in whole, or in part, by the Wellcome Trust. For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission.",

year = "2021",

month = oct,

day = "4",

doi = "10.1038/s41398-021-01568-4",

language = "English",

volume = "11",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task

AU - de Cates, Angharad

AU - Wright, Lucy C.

AU - Martens, Marieke A.G.

AU - Gibson, Daisy

AU - Türkmen, Cagdas

AU - Filippini, Nicola

AU - Cowen, Philip J.

AU - Harmer, Catherine J.

AU - Murphy, Susannah E.

N1 - Funding: ANdeC is funded by a Wellcome Trust Clinical Doctoral Research Fellowship (216430/Z/19/Z), and has received a travel grant from the Royal College of Psychiatrists/Gatsby Foundation. MM is and NF was at the time of the study funded by the NIHR Oxford Health Biomedical Research Centre. This research was supported by the NIHR Oxford Health Biomedical Research Centre and by the Wellcome Centre for Integrative Neuroscience (WIN) (203139/Z/16/Z). The views expressed are those of the authors and not necessarily those of Wellcome, the NHS, the NIHR, or the Department of Health. None of these bodies had a significant role in the design, collection and analysis of data, or decision to publish this article. This research was funded in whole, or in part, by the Wellcome Trust. For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission.

PY - 2021/10/4

Y1 - 2021/10/4

N2 - Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT4 partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.

AB - Cognitive deficits commonly accompany psychiatric disorders but are often underrecognised, and difficult to treat. The 5-HT4 receptor is a promising potential treatment target for cognitive impairment because in animal studies 5-HT4 receptor agonists enhance hippocampal-dependent memory processes. To date, there has been little work translating these effects to humans. We tested whether short-term administration of the 5-HT4 partial agonist, prucalopride, modified behavioural and neural (fMRI) memory processing in 44 healthy human volunteers using an experimental medicine model. We found that participants who had received six days of prucalopride treatment were significantly better at recalling previously seen neutral images and distinguishing them from new images. At a neural level, prucalopride bilaterally increased hippocampal activity and activity in the right angular gyrus compared with placebo. Taken together, these findings demonstrate the potential of 5-HT4-receptor activation for cognitive enhancement in humans, and support the potential of this receptor as a treatment target for cognitive impairment.

U2 - 10.1038/s41398-021-01568-4

DO - 10.1038/s41398-021-01568-4

M3 - Article

SN - 2158-3188

VL - 11

JO - Translational Psychiatry

JF - Translational Psychiatry

M1 - 497

ER -