Effect of the sEH inhibitor AUDA on arachidonic acid metabolism and NF-κB signaling of rats with postpartum depression-like behavior

Objective: To investigate whether sEH inhibitor AUDA can mitigate postpartum depression (PPD)-like symptoms in the rat model and regulate the AA/NF-κB pathway to suppress the inflammatory response in the prefrontal lobes of PPD rats.

Methods: Five groups of Sprague Dawley rats were used: normal, sham operated, PPD model, AUDA, and paroxetine hydrochloride. During the 21-day treatment period, Animals in all groups underwent assessments (open field test, forced swimming test, and sucrose consumption) for depression-like behavior. At the conclusion of the treatment period, Animals in all study groups were euthanized and various proteins in the prefrontal lobes were measured.

Results: Depression-like behavior in rats was attenuated by AUDA. In the prefrontal lobes of PPD rats, levels of 5-LOX, COX-2, sEH, IL-1β, IL- 6, p65, p-p65, P-IκBα, NF-κB p65, and GFAP were increased while levels of epoxyeicosatrienoic acids and 5-HT were decreased. AUDA reversed these changes, thus having a similar effect as the classic antidepressant paroxetine hydrochloride.

Conclusion: AUDA may constrain AA/NF-κB in the prefrontal cortex of PPD rats, thus inhibiting the inflammatory response and ultimately attenuating postpartum depression-like behavior.