Delta opioid receptors (DOPs) play a key role in the development of depression and other mental health conditions. Previous research suggests that targeting DOP’s can produce fast results with few adverse side effects compared to existing drugs. One drug in particular, known as KNT-127, has been shown to have significant anti-depressant activity and minimal side effects. Its underlying mechanisms, however, remain unknown.
To understand more about how the drug works, researchers observed its effects in a mouse model of depression. To create the mouse model, they exposed five-week-old male mice to extreme psychological stress for ten minutes per day for ten days. They gave mice repeated doses of KNT-127 during the stressful period and 28 days afterward.
In the end, the researchers found that administering KNT-127 both during and after the stress period protected normal social interaction behaviors and increased serum corticosterone levels- a hormone secreted by mice under stress. KNT-127 also suppressed microglial activation- which normally increases under psychological stress- and thus reduced inflammation in the hippocampus of mice.
The researchers further found that, when administered during the stressful period, KNT-127 protected against stress-induced newborn neuronal death in the hippocampus. By contrast, when administered after stress, KNT-127 did not affect the newborn neuron survival rate. Administration both during and after the stress period did not affect neurogenesis. The researchers suggested that collectively, the above effects exert anti-stress and anti-depressant-like effects.
“Patients with depression often have to face situations where they cannot avoid stressful environments, even during treatment. Therefore, we believe that the additional anti-stress effect during the treatment period has important clinical significance.” said study author Prof. Akiyoshi Saitoh from the Tokyo University of Science in a press release.
“We expect that the successful clinical development of DOP agonists will greatly broaden the options for the treatment of depression in the future,” he concluded.
Sources: Neuroscience News, Neuropharmacology