A role for 5-HT4 receptors in human learning and memory

Background: 5-HT4 receptor stimulation has pro-cognitive and antidepressant-like effectsin animal experimental studies; however this pharmacological approach has not yet been tested in humans. Here we used the 5-HT4 receptor partial agonist prucalopride to assess the translatability of these effects and characterize, for the first time, the consequences of 5-HT4 receptor activation on human cognition and emotion.Methods: 41 healthy volunteers were randomized, double-blind, to a single dose of prucalopride (1mg) or placebo in a parallel groups design. They completed a battery of cognitive tests measuring learning and memory, emotional processing and reward sensitivity.Results: Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task, and increased the probability of choosing a symbol associated with high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks.Conclusions: These findings are a translation of the memory enhancing effects of 5-HT4 receptor agonism seen in animal studies, and lend weight to 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. Contrary to the effects reported in animal models, prucalopride did not reveal an antidepressant profile in human measures of emotional processing