The Effect of the 5-HT4 Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain

Angharad N de Cates; Marieke A G Martens; Lucy C Wright; Cassandra D Gould van Praag; Liliana P Capitão; Daisy Gibson; Philip J Cowen; Catherine J Harmer; Susannah E Murphy

doi:10.3389/fpsyt.2022.859123

The Effect of the 5-HT₄ Agonist, Prucalopride, on a Functional Magnetic Resonance Imaging Faces Task in the Healthy Human Brain

Front Psychiatry. 2022 Apr 12:13:859123. doi: 10.3389/fpsyt.2022.859123. eCollection 2022.

Authors

Angharad N de Cates^{1

2}, Marieke A G Martens^{1

2}, Lucy C Wright^{1

2}, Cassandra D Gould van Praag^{1

3}, Liliana P Capitão^{1

2}, Daisy Gibson^{1

2}, Philip J Cowen^{1

2}, Catherine J Harmer^{1

2

3}, Susannah E Murphy^{1

2}

Affiliations

¹ Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, United Kingdom.
² Oxford Health National Health Service (NHS) Foundation Trust, Warneford Hospital, Oxford, United Kingdom.
³ Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, United Kingdom.

Abstract

Depression is a common and often recurrent illness with significant negative impact on a global scale. Current antidepressants are ineffective for up to one third of people with depression, many of whom experience persistent symptomatology. 5-HT₄ receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore studied the effect of the 5-HT₄ partial agonist prucalopride (1 mg daily for 6 days) on the neural processing of emotional faces in 43 healthy participants using a randomised placebo-controlled design. Participants receiving prucalopride were more accurate at identifying the gender of emotional faces. In whole brain analyses, prucalopride was also associated with reduced activation in a network of regions corresponding to the default mode network. However, there was no evidence that prucalopride treatment produced a positive bias in the neural processing of emotional faces. Our study provides further support for a pro-cognitive effect of 5-HT₄ receptor agonism in humans. While our current behavioural and neural investigations do not suggest an antidepressant-like profile of prucalopride in humans, it will be important to study a wider dose range in future studies.

Keywords: antidepressant; cognition; emotional processing; functional neuroimaging (fMRI); serotonin receptor 4.