Progesterone and fluoxetine treatments of postpartum depressive‐like behavior in rat model

Abstract Research studies have indicated that alterations in plasma progesterone levels might be associated with the hippocampal synaptic plasticity of postpartum depressive‐like behavior. Herein, we assess both progesterone and fluoxetine effects in adult female Sprague‐Dawley rats with postpartum depressive‐like behavior. Depressive‐like behavior of postpartum rats was established using chronic ultra‐mild stress (CUMS) method for 1 week from gestation day 15. Postpartum rats that showed depressive‐like behavior were treated with either progesterone (subcutaneously, 0.5 mg/kg) from gestation day 17 to gestation day 22 or fluoxetine (by gavage, 10 mg/kg/day) for 4 weeks after birth. Open field and sucrose preference tests were conducted at the start, week 2 and week 4 postpartum. Golgi staining, immunofluorescence and Western blot analyses of rats’ hippocampi were conducted on week 4 postpartum. Results showed CUMS increases depressive‐like behavior, however, treatment with progesterone and fluoxetine improves this behavior. Both progesterone and fluoxetine treatments increase the numbers of dendritic spines pyramidal neurons in the CA3 region of the hippocampus as well as protein expression levels of microtubule‐associated protein 2 (MAP‐2) and synaptophysin (SYP). CUMS‐induced decrement of MAP–2 and SYP protein expressions can be prevented by treatment with progesterone in advanced pregnant stage and fluoxetine in the postpartum period.