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What are the effects of Delta opioid receptors?

What are the effects of Delta opioid receptors?

Science News

TOKYO, Japan — In a groundbreaking study published in Neuropsychopharmacology Reports on December 29, 2024, a team of researchers from Tokyo University of Science, led by Professor Akiyoshi Saitoh, has made a significant leap in understanding and potentially treating anxiety-related disorders. This innovative research centers on the delta opioid receptors (DOPs), a critical component in the brain’s emotional regulation system.

The study illuminates the mechanistic roles of these receptors and specific neuronal pathways, particularly focusing on the promising therapeutic effects of a delta opioid receptor agonist known as KNT-127. This compound has shown notable ‘anxiolytic’ or anxiety-reducing effects in animal models, with minimal side effects, marking a potential paradigm shift in how anxiety disorders could be treated.

One of the key findings of the research is the identification of the neuronal network projecting from the ‘prelimbic cortex’ (PL) to the ‘basolateral nucleus of the amygdala’ (BLA). This pathway has been implicated in the development of depression and anxiety-like symptoms. The team’s prior work showed that KNT-127 inhibits the release of glutamate in the PL region, a neurotransmitter playing a pivotal role in anxiety.

To further their understanding, the researchers employed an ‘optogenetic’ mouse model, wherein they implanted a light-responsive chip in the PL-BLA region of mice and activated the neural circuit using light stimulation. Behavioral studies, including the elevated-plus maze (EPM) test and assessments of conditioned fear response, revealed that activation of the PL-BLA pathway leads to innate anxiety-like behavior.

Crucially, treatment with KNT-127 significantly altered these responses, suggesting a reduction in anxiety-like behavior induced by the specific activation of the PL-BLA pathway. This finding opens the door to new, targeted therapies with rapid action and fewer side effects, a much-needed advancement in the field.

Professor Saitoh is optimistic about the clinical implications of this research. Given that the brain neural circuits focused on in this study are conserved in humans, and the PL-BLA region is overactive in patients with depression and anxiety disorders, there is a strong potential that suppressing overactivity in this brain region using DOP-targeted therapies can exert significant anxiolytic effects in humans.

This study not only enhances our understanding of the neural and molecular mechanisms triggering anxiety but also paves the way for the development of novel, effective treatments for anxiety-related disorders. The Tokyo University of Science team’s work could mark a turning point in mental health treatment, offering hope to millions suffering from these debilitating conditions.

Full Paper:

The delta opioid receptor agonist KNT‐127 relieves innate anxiety‐like behavior in mice by suppressing transmission from the prelimbic cortex to basolateral amygdala – Kawaminami – Neuropsychopharmacology Reports – Wiley Online Library

Tokyo University of Science