Philadelphia [US], June 13 : Debilitating cognitive deficiencies frequently accompany mood disorders and other mental illnesses. There are presently few therapies available, however research in both animals and people has suggested that medications that stimulate serotonin receptors, such the laxative prucalopride, may be effective in treating the symptoms. But how the drug impacts the brain's resting activity has remained a mystery.
The effects of the medication are investigated in a recent research in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier.
In regions of the brain, such as the frontal cortex, basal ganglia, and hippocampus, which are known to impact cognitive function and regulate mood, serotonin receptors, and the 5-HT4-type receptors in particular, are present. Antidepressant drugs' main targets are serotonin receptors, although treating mood disorders frequently doesn't treat cognitive problems.
The researchers enlisted 50 healthy volunteers, half of whom received a six-day course of prucalopride, a highly selective agonist of the 5-HT4 type serotonin receptor, whereas the other half of the participants received a placebo. Participants underwent scanning with functional magnetic resonance imaging, including a "resting scan," in which they relaxed in the scanner.
Lead author Angharad de Cates, PhD, MRCPsych, at the University of Oxford, said of the work, "Our previous studies on prucalopride demonstrated that even at low clinical doses it can improve cognition and memory in healthy volunteers. This latest research provides a neurological mechanism by which this might occur."
Participants who received the medication displayed more functional connectivity in their resting-state (rsFC) between major cognitive networks. This included more rsFC between the central executive network, a brain network used for processing thoughts, and the posterior and anterior cingulate cortex (ACC), brain areas that regulate information processing and attention in the brain. There was also more rsFC between regions of the ACC and the lateral occipital cortex, a region that helps us pay attention to objects that matter. In addition, medicated participants compared to placebo controls showed decreased rsFC in the default mode network, a brain network that is activated during mind wandering.
Dr. de Cates added, "This provides further evidence that prucalopride is having an effect in areas of the brain that improve cognitive function - both by increasing and reducing connectivity between specific brain regions as required."
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