The Role of the Oxytocinergic System in the Pathophysiology of Peripartum Depression: Insights from a Murine Model

Peripartum depression (PPD) is a severe and often underdiagnosed mood disorder that affects approximately 10–20% of women globally and has profound consequences for both mothers and their offspring. Beyond maternal suffering, PPD disrupts mother–infant bonding, alters the early-life social environment, and increases the risk of neurodevelopmental disorders in children. Only two medications are currently approved specifically for PPD, but their accessibility and effectiveness remain limited. Progress in treatment development is stalled by the scarce knowledge of the neurobiological mechanisms underlying PPD. Given the critical role of oxytocin (OXT) during labour, lactation, maternal care and social bonding, our aim is to evaluate the role of OXT in PPD pathophysiology using a mouse model of PPD. To address this question, we implemented a stress-based model of PPD, combining chronic mild unpredictable stress and maternal separation during pregnancy and postpartum in order to induce a depressive-like phenotype. Our findings show that this model induces depressive-like behaviors, together with deficits in sociability and maternal care. Using cFOS immunostaining as a proxy of neuronal activation, we observed a lower percentage of active OXT+ cells in the paraventricular nucleus of the hypothalamus in the PPD group compared to control dams. These findings suggest that altered OXT activity may contribute to PPD pathophysiology and highlight a potential target for future research.