A novel study reveals that prucalopride, a routinely used laxative, boosts cognitive abilities and memory in healthy subjects by influencing resting brain activity. It unveils that prucalopride strengthens the connectivity of cognitive networks while reducing mind-wandering, suggesting a possible treatment avenue for cognitive deficits and depressive symptoms.
A cognitive enhancement agent could potentially hold therapeutic benefits.
Cognitive issues often appear in conjunction with mood disorders and other mental health conditions, often leading to considerable challenges. The present treatment options are quite limited, but research on animals and humans implies that medications like prucalopride, a laxative that triggers serotonin receptors, might offer therapeutic advantages for these symptoms. Nonetheless, how this drug affects resting brain activity is yet to be understood. Fresh research published by Elsevier in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging explores the drug’s effects on healthy adult subjects.
Serotonin receptors, especially the 5-HT4 type, are distributed throughout various brain regions like the frontal cortex, basal ganglia, and hippocampus, all playing pivotal roles in cognitive functioning and mood regulation. Serotonin receptors are the primary targets of antidepressant drugs, but treating mood disorders doesn’t necessarily relieve cognitive symptoms.
The study involved 50 healthy subjects, with half of them taking prucalopride, a highly selective 5-HT4 type serotonin receptor agonist, for six days, and the remaining half receiving a placebo. Participants underwent functional magnetic resonance imaging scans, including a “resting scan” where they simply relaxed in the scanner.
Angharad de Cates, Ph.D., MRCPsych, from the University of Oxford and the lead author of the study, stated, “Our prior work on prucalopride illustrated that even at low clinical doses, it can boost cognition and memory in healthy subjects. Our latest study offers a neurological mechanism that may explain this.”
The study discovered that the healthy subjects who took prucalopride demonstrated increased functional connectivity within key cognitive regions and a primary cognitive network. Image Credit: de Cates, et al., Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.
Subjects who took the medication exhibited enhanced resting-state functional connectivity (rsFC) between significant cognitive networks, including an increase in rsFC between the central executive network and the posterior and anterior cingulate cortex (ACC), which regulate information processing and attention. There was also heightened rsFC between regions of the ACC and the lateral occipital cortex, a region crucial for focusing on relevant objects. Moreover, those on the medication, compared to placebo, showed decreased rsFC in the default mode network, a network active during mind-wandering.
Dr. de Cates explained, “This additional evidence suggests that prucalopride impacts areas of the brain that enhance cognitive function by both augmenting and reducing connectivity between specific brain regions as necessary.”
Susannah Murphy, Ph.D., Associate Professor and co-senior author of the study, noted, “Optimal connectivity between and within these brain networks is crucial for proper thinking, and this connectivity is often abnormal in depression. Those taking prucalopride scored better on cognitive tests on the day of the scan compared to placebo participants. This implies that the rsFC changes we observed with prucalopride might act as a ‘signature’ of a cognition-enhancing drug.”
Dr. Murphy added, “Untreated cognitive issues significantly affect the life quality of individuals with depression. This research builds on the expanding evidence that drugs influencing the 5-HT4 serotonin receptor hold promise for a new way to treat depression and cognitive deficits.”
Catherine Harmer, Ph.D., Professor of Cognitive Neuroscience and co-senior author of the study, mentioned, “This research builds on the body of evidence that the common laxative treatment prucalopride has significant effects on the brain, especially on circuits crucial for learning and memory. Together with prior data, this indicates that this drug might serve as a cognitive enhancement treatment in conditions like depression.”
Cameron Carter, MD, Editor of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, commented, “These findings, showcasing the modulation of resting state connectivity in the brain by the 5-HT4 receptor agonist and potential cognitive enhancer prucalopride, build on prior evidence that the agent modulates brain systems engaged during focused, high-level cognitive activity, hinting at possible therapeutic benefits.”
Reference: “5-HT4 Receptor Agonist Effects on Functional Connectivity in the Human Brain: Implications for Procognitive Action” by Angharad N. de Cates, Marieke A.G. Martens, Lucy C. Wright, Daisy Gibson, Gershon Spitz, Cassandra D. Gould van Praag, Sana Suri, Philip J. Cowen, Susannah E. Murphy and Catherine J. Harmer, 23 April 2023, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. DOI: 10.1016/j.bpsc.2023.03.014
Frequently Asked Questions (FAQs) about Prucalopride cognitive enhancement
What is the main finding of the study?
The study found that prucalopride, a common laxative, improves cognitive function and memory in healthy volunteers by altering resting brain activity.
How does prucalopride enhance cognitive function according to the study?
Prucalopride enhances connectivity between cognitive networks and reduces mind-wandering activity, suggesting a potential treatment path for cognitive impairment and depression symptoms.
What is prucalopride typically used for?
Prucalopride is typically used as a laxative. It acts by stimulating serotonin receptors in the body.
What role do serotonin receptors play in the brain?
Serotonin receptors, particularly the 5-HT4 type, are distributed throughout various brain regions and play a critical role in cognitive functions and mood regulation.
How was the research conducted?
The researchers enlisted 50 healthy volunteers. Half received a six-day course of prucalopride, whereas the other half received a placebo. Participants underwent scanning with functional magnetic resonance imaging, including a resting scan.
What did the researchers find about prucalopride’s impact on brain connectivity?
Participants who received prucalopride showed increased resting-state functional connectivity (rsFC) between major cognitive networks. They also showed decreased rsFC in the default mode network, which is activated during mind wandering.
Could prucalopride be used as a treatment for cognitive impairments and mood disorders?
The study suggests potential therapeutic benefits of prucalopride for cognitive impairments and mood disorders, but more research is needed before it can be considered as a treatment option.
More about Prucalopride cognitive enhancement
- Effects of Prucalopride on Brain Activity
- Cognitive Enhancement via Prucalopride
- Understanding Serotonin Receptors