Millions of people worldwide suffer from depression caused by psychological stress, but most of the available anti-depressant drugs are slow, prone to resistance, and have serious side effects. This calls for more effective treatment options. Delta opioid receptors (DOPs) have been found to play a significant role in the development of depression, and DOP agonists have shown better efficacy and fewer side effects than most existing anti-depressant drugs. KNT-127 is a potent DOP agonist that acts quickly with minimal side effects, but its mechanism of action is not yet fully understood.

To investigate the underlying mechanism of action of KNT-127, a team of researchers from Tokyo University of Science and the University of Tsukuba evaluated its therapeutic and preventive effects in a mouse model of depression. The researchers exposed male mice to extreme psychological stress for ten days to create the depression mouse model, followed by administering KNT-127 during and after the stress period. They found that KNT-127 significantly improved social interaction, reduced serum corticosterone levels, and suppressed microglial activation and inflammation in the hippocampus of the mice.

KNT-127 was found to prevent neuronal inflammation and reduce newborn neuronal death without affecting neuron formation, exerting anti-stress and anti-depressant-like effects during and post-stress periods, respectively. This study suggests that KNT-127 may offer additional benefits to patients during treatment by reducing stress. The researchers hope that the clinical development of DOP agonists will provide a more extensive range of treatment options for depression in the future.

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Source: Science Daily