Activation of the Oxytocin System in the Hypothalamic Paraventricular Nucleus Improves Stress-Induced Postpartum Depression-Like Behavior in Rats

Abstract

Background: Oxytocin (OT) is a key molecule that not only acts as a uterine-contracting hormone during delivery but is also a critical maternal hormone that enables the social transmission of maternal behavior. Postpartum depression (PPD) is a series of depression-like symptoms that occur especially in women in the perinatal period and is accompanied by the failure to adapt to motherhood as well as impaired parent-infant bonding. However, the mechanism by which OT regulates PPD is still unclear. This study aimed to investigate the correlation between OT levels in the paraventricular nucleus (PVN) and PPD and to explore the potential mechanism underlying the involvement of the OT system in the regulation of PPD. 

Methods: We induced perinatal chronic stress in pregnant rats to establish a PPD model. OT levels in the cerebrospinal fluid (CSF) and PVN were measured throughout the perinatal period. We administered the chemogenetic virus hM3Dq into the PVN, intraperitoneally injected N-oxyclozapine to activate OT-secreting neurons, and observed the effects of OT treatment on behaviors related to PPD. Finally, we investigated the potential mechanism underlying PPD regulation by the OT system via transmission electron microscopy, immunofluorescence (IF), and quantitative real-time PCR (qRT-PCR). 

Results: Compared with those in the normal group, CSF oxytocin levels in the postpartum depression group decreased from late pregnancy to lactation (p < 0.001). Chemogenetic activation-induced endogenous OT release in the PVN not only alleviated PPD-like symptoms in rats but also enhanced the intracellular production of OT. Transmission electron microscopy revealed an increase in the size of the Golgi apparatus, endoplasmic reticulum, and dense vesicles within OT neurons. IF and qRT-PCR revealed elevated OT levels and increased oxytocin expression within the PVN following chemogenetic activation (p < 0.01). 

Conclusion: Lower OT levels are strongly associated with the occurrence of PPD. The release of activated OT has been shown to improve PPD-like behaviors in rats and promote intracellular OT synthesis.