Interactive impacts of social deprivation and intranasal oxytocin administration on oxytocin receptor density in prairie vole brains

Introduction Early-life social experiences have a profound impact on the development of the brain and behavior. Previous work has shown that prairie voles ( Microtus ochrogaster ) raised in a socially limited environment (raised by a single mother and isolated after weaning) engaged in more social behaviors compared to those raised in a socially enriched environment (raised biparentally and group-housed after weaning). Furthermore, intranasal oxytocin has been therapeutically used in children, yet little is known about how this might affect brain development. Oxytocin is a crucial neuropeptide involved in social behavior and cognition, and variation in parental care and early social experiences has the potential to alter oxytocin receptors (OTR) throughout the brain. However, few studies have asked how different social experiences interact to alter brain phenotype. Methods In this study, male prairie voles were raised in either a socially limited condition (raised by a single mother and isolated after weaning) or raised in a socially enriched condition (raised biparentally and group housed after weaning). Subjects in each condition were also administered either intranasal oxytocin or saline (PND 21-42). Finally, brains were collected, and we used autoradiography to quantify OTR throughout the brain of these animals. Results It showed that much of the forebrain did not show differences in OTR density as a result of either manipulation, reinforcing the idea that OTR phenotype is generally resistant to external forces. However, we found two important exceptions to this theme in the prefrontal cortex and the lateral septum – two areas of the brain that are critical to social behavior in general and prairie vole pair bonding in particular. Specifically, socially limited animals had significantly more OTR in the prefrontal cortex compared to socially enriched animals, and subjects administered intranasal oxytocin during adolescent development expressed more OTR in the lateral septum compared those treated with saline. Discussion Although the impacts of external sources on OTR density appear to be restricted to only a few locations in the brain, these brain regions are central to social functioning, indicating limited but potentially significant impacts on social behaviors are plausible.