Oxytocin receptor or vasopressin 1a receptor knockout suppresses same-sex conspecific aggression without affecting partner preference in male prairie voles (Microtus ochrogaster).

Aggressive behavior toward unfamiliar conspecifics is a feature of pair-bonded male prairie voles (Microtus ochrogaster). Although oxytocin (OXT) and arginine vasopressin (AVP) signaling have been implicated in social behaviors in research using pharmacological manipulations, their contributions to aggression are not fully understood. Here, we generated vasopressin 1a receptor knockout (V1aR KO) prairie voles using CRISPR/Cas9-mediated genome editing and compared their aggressive behavior with that of oxytocin receptor knockout (OXTR KO) and wildtype (WT) males. Functional loss of V1aR was confirmed by in vitro receptor assays and autoradiography. Following partner formation, males were assessed for aggression toward a male stranger, a female stranger, and their female partner, as well as for partner preference and social interaction. WT males exhibited robust and selective aggression toward male strangers, characterized by prolonged aggressive bouts and frequent biting, while rarely showing aggression toward their partners. In contrast, both V1aR KO and OXTR KO males displayed a marked reduction in aggression toward male strangers. Notably, partner preference and social investigation were preserved in both knockout lines. These findings provide genetic evidence that both V1aR and OXTR signaling are critical for the expression of same-sex conspecific aggression in male prairie voles. The suppression of same-sex aggressive behavior without affecting pair bonding in V1aR KO and OXTR KO voles highlights the distinct roles of OXT and AVP in social behaviors of prairie voles.