Intranasal Oxytocin and Social Deprivation Interact to Alter Oxytocin Receptor Density in Prairie Vole Brains

Early-life social experiences profoundly impact brain development and social behavior. Prairie voles serve as a model for sociality, where socially limited environments can lead to altered social behaviors. While intranasal oxytocin is explored therapeutically in children, its impact on brain development, particularly oxytocin receptor (OTR) distribution, remains poorly understood. Oxytocin is a crucial neuropeptide for social cognition, and variations in early social experiences are known to alter OTR expression. However, the interactive effects of different social experiences and exogenous oxytocin on brain phenotype, specifically OTR density, represent a critical knowledge gap.

Male prairie voles were raised under two conditions: socially limited (single mother, isolated post-weaning) or socially enriched (biparental, group-housed post-weaning). Within each condition, subjects received either intranasal oxytocin or saline daily from PND 21-42. Brains were subsequently collected to quantify OTR density using autoradiography. This design allowed for the examination of interactive impacts between early social environment and adolescent oxytocin administration on OTR distribution across various brain regions.

While much of the forebrain showed no significant differences in OTR density due to either social manipulation or oxytocin administration, two key regions exhibited notable changes. These exceptions were the prefrontal cortex and the lateral septum, both critical for general social behavior and prairie vole pair bonding. Specifically, socially limited animals displayed significantly more OTR in the prefrontal cortex compared to socially enriched animals. Furthermore, subjects administered intranasal oxytocin during adolescent development expressed more OTR in the lateral septum. This suggests a region-specific sensitivity of OTR phenotype to the combined effects of early social environment and exogenous oxytocin.

Socially limited prairie voles had significantly more OTR in the prefrontal cortex than socially enriched animals.