Scientists identify potential new therapeutic target for anxiety

Neurons

A new study has highlighted the role of specific neuronal circuits in the brain involved in the development of anxiety, and distinct mechanisms of action of the therapeutic delta opioid receptor (DOP) agonist KNT-127.

Understanding the neural circuits and molecular mechanisms that trigger anxiety can aid in the development of effective targeted pharmacological treatments.

DOPs, which localise in the regions of the brain associated with emotional regulation, play a key role in the development of anxiety.

Several studies have demonstrated the therapeutic effects of DOP agonists (synthetic compounds which selectively bind to DOPs and mimic the effect of the natural binding compound) in a wide range of behavioural disorders.

One such selective DOP agonist – KNT-127 – has been shown to exert ‘anxiolytic’ or anxiety-reducing effects in animal models, with minimal side effects. However, its mechanism of action is not clearly understood, thereby limiting its widespread clinical application.

To bridge this gap, Professor Akiyoshi Saitoh, with Ayako Kawaminami and a team from the Tokyo University of Science, Japan, conducted a series of experiments and behavioural studies in mice.

Their study has revealed the role of the ‘prelimbic cortex-basolateral nucleus of the amygdala’ (PL-BLA) neuronal axis in the regulation of innate anxiety, and its potential function in DOP-mediated anxiolytic effects.

However, further studies are needed to understand the precise underlying molecular and neuronal mechanisms, for the development of novel therapies targeting DOP in the PL-BLA pathway.

Professor Saitoh said: “The brain neural circuits focused on in this study are conserved in humans, and research on human brain imaging has revealed that the PL-BLA region is overactive in patients with depression and anxiety disorders. We are optimistic that suppressing overactivity in this brain region using DOP-targeted therapies can exert significant anxiolytic effects in humans.”

Diana Spencer, Senior Digital Content Editor, DDW

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