Chair: Professor Michael Browning

Abstract: Animal experimental studies suggest that 5-HT₄ receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT₄ receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. 5-HT₄ receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. Until recently, the translation of these effects to humans has been challenging. Establishing the cognitive effects of compounds targeting the 5-HT₄ receptor in humans is particularly important in light of the limited predictive validity of animal models and the disappointing failure to predict the efficacy of pro-cognitive and antidepressant drugs in humans from drug discovery studies in rodents. We have recently conducted a series of human experimental studies characterising the effects of prucalopride, a partial 5-HT₄ receptor agonist, on cognitive biomarkers related to depression and cognition. In this talk I will present the findings from this work, which support the idea that the 5-HT₄ receptor could be an innovative target for the treatment of cognitive deficits associated with depression and other neuropsychiatric disorders. This work is an example of how human neurocognitive models can be usefully applied to the drug development pathway.