We have previously shown that a single dose of a TREK-1 channel activator, ostruthin, exhibited antidepressant and anxiolytic effects Shirt in acute behavioral test models in mice.To assess the potential clinical application, it is essential to evaluate the effects of long-term administration of ostruthin in a chronically stressed mouse model, which is considered to be similar to the clinical condition of major depression in humans.Here, we tested the effects of a single and a 7-day administration of ostruthin on mice that were subjected to chronic unpredictable mild stress (CUMS).
A single administration of ostruthin showed antidepressive effects in the tail suspension and forced swim tests of CUMS-treated mice.Unexpectedly, the 7-day administration exhibited only insignificant antidepressive and anxiolytic effects.The 7-day regimen click here did not affect food intake or body-weight gain, suggesting the absence of apparent cytotoxicity.
The mice receiving the 7-day administration had significantly lower blood concentrations of ostruthin compared to those receiving a single dose, suggesting an upregulation of drug-metabolizing activities.These findings suggest that there is a need for stable TREK-1 channel activators that are not affected by drug metabolism.