Early-life Oxytocin Attenuates the Social Deficits Induced by Caesarean-section Delivery in the Mouse

The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 μg/20 μl; s.c.) or saline daily from postnatal days 1-5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.