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 Martens, Lucy Wright, Cassandra Gould van Praag, Liliana Capitão, Daisy Gibson, Philip J. Cowen, Catherine J. Harmer, Susannah E. Murphy
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-HT 4 receptor agonists show promise in both animal models of depression and cognitive deficit. We therefore studied the effect of the 5-HT 4 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-HT 4 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.