PROMOTE: Effects of 5-HT4 Agonism on Cognition and Sleep in Peopl With Low Mood

Serotonin is a chemical in the brain that plays an important role in mood, sleep, and other functions. It works by attaching to different types of serotonin receptors on brain cells. These receptors act like "locks", with serotonin acting like a "key". Different types of serotonin receptors have different effects in the brain. Prucalopride is a licensed medication used to treat constipation. It acts on a particular serotonin receptor, called the serotonin 4 receptor. Researchers are interested in this receptor because understanding how it works in the brain may help us learn more about depression and could contribute to the development of new treatments in the future. The purpose of this study is to investigate the effects of prucalopride in people experiencing low mood. We will compare prucalopride with a placebo (a treatment with no active medication) to find out whether activating the serotonin 4 receptor affects sleep and aspects of thinking, including memory, attention and decision making.

Inclusion Criteria: * Aged between 18-65 * Male or female * Participant is willing and able to give informed consent for participation in the research * Body mass index in the range of 18-35 inclusive * Current PHQ-9 score in the range of 9-15 Exclusion Criteria: * Any current or previous episode of a severe mental illness, other than Depressive Disorder. Comorbid Anxiety disorders will be allowed, but not OCD or PTSD. * A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia * Body Mass Index outside the range of 18 to 35 inclusive * Any significant current medical condition likely to interfere with conduct of the study or analysis of data * Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion) * Ongoing psychopharmacological treatment for depression, including hypnotics (psychotherapy will be allowed as long as not newly-started in the last 6 weeks) * High consumption of illicit substances to an extent that would make complying with study protocol challenging (including alcohol, caffeine, nicotine) * Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study * Currently pregnant, trying to get pregnant, or breast feeding * Current, or a significant history of, gastro-intestinal disorder or irritable bowel syndrome * Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose * Participation in a study that involves the use of a medication or novel vaccine within the last three months * Participation in a study using the same tasks in the last year * Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging, including yellow/blue colourblindness * A head injury causing concussion or loss of consciousness within the last six months * Moderate to high risk of suicide or self-harm * Participant who is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Chief Investigator. Additional Exclusion Criteria for Participants in the Sleep Study Cohort: * Unable to undergo cardiac monitoring * Unable to wear the sleep patch device for full monitoring period * Implanted neurostimulator or pacemaker