Duan_2023_J.Neuroimmunol_385_578250

OBJECTIVE: To investigate whether sEH inhibitor AUDA can mitigate postpartum depression (PPD)-like symptoms in the rat model and regulate the AA/NF-kappaB 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-1beta, IL- 6, p65, p-p65, P-IkappaBalpha, NF-kappaB 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-kappaB in the prefrontal cortex of PPD rats, thus inhibiting the inflammatory response and ultimately attenuating postpartum depression-like behavior.