summary: A new study investigated how the laxative prucalopride, known to activate serotonin receptors, affects resting brain activity in healthy adults.
This study found that people who took prucalopride had increased functional connectivity between key cognitive networks at rest. This change provides a potential neurological mechanism by which prucalopride may enhance cognition and memory.
The results support prucalopride and agents that affect 5-HT4 serotonin receptors as potential treatments for depression and cognitive impairment.
- Prucalopride is primarily a laxative and at low doses it also improves cognition and memory.
- This drug strengthens connections in the brain and helps with attention and information processing.
- Conversely, the connectivity of the brain’s default mode network was reduced, adjusting cognitive function as needed.
Cognitive disorders are accompanied by mood disorders and other mental illnesses, often with debilitating effects.
Current treatments are limited, but animal and human studies point to drugs such as the laxative prucalopride, which activates serotonin receptors, as potential treatments for the condition. there is However, it remains unclear how the drug affects resting brain activity.
Now, new research Biological Psychiatry: Cognitive Neuroscience and Neuroimagingto examine the effects of drugs in healthy adults.
Serotonin receptors and 5-HTFourIn particular, α-type receptors are present in regions throughout the brain, including the frontal cortex, basal ganglia, and hippocampus, and are known to mediate cognitive function and regulate mood.
Serotonin receptors are the primary targets of antidepressants, but resolving mood disorders often does not resolve cognitive symptoms.
The researchers recruited 50 healthy volunteers, half of whom received six days of prucalopride, a highly selective agonist of 5-HT.Four The other half of the participants received a placebo.
Participants underwent functional magnetic resonance imaging scans, including a ‘rest scan’ in which they relaxed in the scanner.
The lead author, Dr. Anharad de Catès, MRCPsych, University of Oxford, said of the study: This latest study provides a neurological mechanism by which this may occur. “
Medication-treated participants showed more functional connectivity between key cognitive networks in the resting state (rsFC).
This includes a more complex network between the central executive network, the brain network used to process thoughts, and the posterior and anterior cingulate cortex (ACC), brain regions that control information processing and attention in the brain. It contained many rsFCs.
Also, there were more rsFCs between the ACC and areas of the lateral occipital cortex, areas that help us pay attention to important objects.
Furthermore, drug-treated participants showed a reduction in rsFC in the default mode network (the brain network activated during mind wandering) compared to placebo controls.
Dr. de Cates added: “This provides further evidence that prucalopride exerts cognitive-improving effects in brain regions by increasing or decreasing connectivity between specific brain regions as appropriate. “
Susannah Murphy, Ph.D., associate professor and co-lead author of the study, said: “Proper connectivity between and within these brain networks is required to think properly, and depression has shown that this connectivity is abnormal.
“Here, participants taking prucalopride scored better on the day-of-scan cognitive tests compared to placebo participants. It suggests that it may serve as a “feature” of improving drugs. “
Dr. Murphy continued, “Untreated cognitive impairment has a significant impact on the quality of life of people with depression.
“This study further strengthens the evidence base that drugs affect 5-HT.Four Serotonin receptors are a promising new way to treat depression and cognitive impairment. ”
“This study shows that prucalopride, a common laxative drug, has important effects on the brain, particularly learning and learning,” said Katherine Hamer, Ph.D., professor of cognitive neuroscience and co-lead author of the study. It further strengthens the evidence base that it can affect important circuits.” memory.
“Together with previous data, we suggest that this drug may be useful as a cognitive-enhancing treatment for disorders such as depression.”
Cameron Carter, MD, Editor Biological Psychiatry: Cognitive Neuroscience and Neuroimagingsaid of the study: “These data show that 5HT modulates resting-state connectivity in the brain.”Four Prucalopride, a receptor agonist and putative cognition enhancer, adds to previous evidence that the drug modulates brain systems involved during intense, high-level cognitive activities and has therapeutic potential. be. ”
About this neuropharmacology, serotonin, and cognitive research news
author: Eileen Leahy
contact: Eileen Leahy – Elsevier
image: Image credited to Neuroscience News
Original research: open access.
“5-HT4 receptor agonists affect functional connectivity in the human brain.Effect on cognition enhancementby Angharad de Cates et al. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
5-HT4 receptor agonists affect functional connectivity in the human brain.Effect on cognition enhancement
Cognitive impairment is often comorbid with mood disorders and can lead to significant functional impairment even after the main mood symptoms have resolved. Currently, there are no pharmacological treatments that adequately address these deficiencies. 5-HTFour Receptor agonists have shown promise as potential cognitive enhancers in animal and early human translational studies. Optimal human cognitive performance is directly related to proper functional connectivity between specific resting-state neural networks.However, so far the effect of 5-HT isFour Receptor agonism for resting-state functional connectivity in the human brain is unknown.
We collected resting-state fMRI scans from 50 healthy volunteers. Twenty-five of them were on her 1 mg prucalopride (highly selective 5-HT) he was on for 6 days.Four 25 subjects who received a receptor agonist) and a placebo in a randomized, double-blind design.
Network analysis confirmed that participants in the prucalopride group had enhanced resting state functional connectivity (rsFC) between the central executive network (cEN) and the posterior cingulate cortex/anterior cingulate cortex (PCC/ACC). I was. Seed analysis also showed increased rsFC between the left and right rostral ACC and left occipital cortical ACC and decreased rsFC between the hippocampus and other default mode network regions.
Similar to other cognition-enhancing drugs, administration of low-dose prucalopride to healthy volunteers appears to enhance rsFC between regions involved in cognitive networks and decrease rsFC within the DMN. This suggests a mechanism of behavioral cognitive enhancement previously seen with 5-HT.Four Human receptor agonist and support potential for 5-HT.Four A receptor agonist used in the psychiatric clinical population.