Déjà-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 pro...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group
2021-10-01
|
Series: | Translational Psychiatry |
Online Access: | https://doi.org/10.1038/s41398-021-01568-4 |
id |
doaj-d7753ba1fec942c5b17a086a3665f019 |
---|---|
record_format |
Article |
spelling |
doaj-d7753ba1fec942c5b17a086a3665f0192021-10-10T11:12:20ZengNature Publishing GroupTranslational Psychiatry2158-31882021-10-011111910.1038/s41398-021-01568-4Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory taskAngharad N. de Cates0Lucy C. Wright1Marieke A. G. Martens2Daisy Gibson3Cagdas Türkmen4Nicola Filippini5Philip J. Cowen6Catherine J. Harmer7Susannah E. Murphy8Department of Psychiatry, University of Oxford, Warneford HospitalDepartment of Psychiatry, University of Oxford, Warneford HospitalDepartment of Psychiatry, University of Oxford, Warneford HospitalDepartment of Psychiatry, University of Oxford, Warneford HospitalDepartment of Psychiatry, University of Oxford, Warneford HospitalIRCCS San Camillo HospitalDepartment of Psychiatry, University of Oxford, Warneford HospitalDepartment of Psychiatry, University of Oxford, Warneford HospitalDepartment of Psychiatry, University of Oxford, Warneford HospitalAbstract 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.https://doi.org/10.1038/s41398-021-01568-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Angharad N. de Cates Lucy C. Wright Marieke A. G. Martens Daisy Gibson Cagdas Türkmen Nicola Filippini Philip J. Cowen Catherine J. Harmer Susannah E. Murphy |
spellingShingle |
Angharad N. de Cates Lucy C. Wright Marieke A. G. Martens Daisy Gibson Cagdas Türkmen Nicola Filippini Philip J. Cowen Catherine J. Harmer Susannah E. Murphy Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task Translational Psychiatry |
author_facet |
Angharad N. de Cates Lucy C. Wright Marieke A. G. Martens Daisy Gibson Cagdas Türkmen Nicola Filippini Philip J. Cowen Catherine J. Harmer Susannah E. Murphy |
author_sort |
Angharad N. de Cates |
title |
Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task |
title_short |
Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task |
title_full |
Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task |
title_fullStr |
Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task |
title_full_unstemmed |
Déjà-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task |
title_sort |
déjà-vu? neural and behavioural effects of the 5-ht4 receptor agonist, prucalopride, in a hippocampal-dependent memory task |
publisher |
Nature Publishing Group |
series |
Translational Psychiatry |
issn |
2158-3188 |
publishDate |
2021-10-01 |
description |
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. |
url |
https://doi.org/10.1038/s41398-021-01568-4 |
work_keys_str_mv |
AT angharadndecates dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT lucycwright dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT mariekeagmartens dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT daisygibson dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT cagdasturkmen dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT nicolafilippini dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT philipjcowen dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT catherinejharmer dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask AT susannahemurphy dejavuneuralandbehaviouraleffectsofthe5ht4receptoragonistprucaloprideinahippocampaldependentmemorytask |
_version_ |
1716829939774259200 |