Oxytocin/Oxytocin Receptor Modulation of Social Odor Investigation in Juvenile Mice

In juvenile mice (P28-P41), social interactions between conspecifics are especially rewarding and necessary for species-typical development. These interactions are rarely aggressive or involve mating and may be ideal to better understand the underlying approach/avoid dilemma for sociability, uncontaminated by sexual or aggressive motivators. Mice must strike a balance between motivated approach behaviors and vigilant threat assessment. In adults, there is a role for the oxytocin receptor (OXTR) to increase motivation to explore and to discriminate threat. It is less clear what role the OXTR plays in aspects of social salience in juveniles. In this study, we tested the genetic contribution of Oxtr in male and female juvenile mice in investigation behavior toward same-sex social odor stimuli. Juvenile (P40-41) mice (Oxtr^+/+, Oxtr^+/-, Oxtr^-/-) were exposed to the soiled bedding of same-sex adults with (OXTwτ) and without (OXTκο) oxytocin in a three-chamber social-odor interaction test. We conducted repeated measures ANOVAs to determine effects of sex and genotype on frequency and duration of behaviors toward OXTwτ- and OXTκο-soiled bedding, including olfactory investigation, stretch-attend posture, and orienting at a distance (i.e., vigilance). Between-subjects main effects demonstrated that juvenile male mice show heightened frequency and duration of total investigation of the bedding stimuli, while female mice displayed greater frequency of total vigilance behavior toward the bedding stimuli. An interaction of sex and genotype was evident with duration of orienting, with Ox^tr+/- males showing reduced total orienting durations. Within-subjects analysis demonstrated a main effect of bedding type, with all juveniles spending more time investigating the OXTwτ bedding than the OXTκο bedding. This bedding effect on duration of investigation did not depend on the Oxtr genotype or sex of the juvenile. In contrast, there was a significant bedding type x genotype x sex interaction for frequency of investigation, with Ox^tr+/- males showing a very strong preference for OXTwτ bedding. These data begin to show oxytocin's modulatory role in approach-avoidance and sex-specific effects on juvenile behavior.