Nonlinear and sex-specific effects of V1aR deletion on juvenile social behavior

Social behaviors emerge during juvenile development and require the integration of social motivation, recognition, and context-appropriate responses. Arginine vasopressin signaling through the V1a receptor (V1aR) has been implicated in multiple aspects of social behavior, yet its role across distinct behavioral domains, developmental stages, and sexes remains poorly understood.

We used a CRISPR/Cas9-generated V1aR knockout model in Syrian hamsters to examine the effects of V1aR disruption on social interaction, social recognition, and social avoidance in juvenile males and females. Hamsters were tested during the peripubertal period (postnatal days 35-36), prior to the onset of stable estrous cyclicity in females.

In a dyadic social interaction assay, V1aR deletion increased social investigation, particularly anogenital investigation, in knockout animals, whereas heterozygous males exhibited reduced locomotor activity and increased self-directed behaviors. In a social odor recognition task, heterozygous animals failed to discriminate between familiar and novel conspecific odors at a 20-min interval, while wild-type and knockout animals showed intact recognition. No odor discrimination or genotype-dependent differences were observed at a 24-h interval, indicating limited evidence of long-term retention across groups. Following social defeat, heterozygous males displayed increased social avoidance, spending less time near an aggressor and more time in the avoidance zone compared with other groups.

Together, these findings reveal domain-specific and nonlinear effects of V1aR disruption on juvenile social behavior, with heterozygous animals exhibiting the most pronounced alterations. These results suggest that V1aR contributes to social behavior in a nonlinear, genotype-dependent, and context-dependent manner and highlight the importance of developmental stage and sex in shaping vasopressin-dependent social processes.