Oxytocin receptor or vasopressin 1a receptor knockout suppresses same-sex aggression in male prairie voles

Aggressive behavior towards unfamiliar conspecifics is a well-documented feature in pair-bonded male prairie voles (Microtus ochrogaster), a model species for social bonding. While oxytocin (OXT) and arginine vasopressin (AVP) signaling are known to influence social behaviors, their precise contributions to aggression, particularly through specific receptor pathways, remain incompletely understood. Current pharmacological studies offer insights, but genetic evidence is crucial to delineate the distinct roles of these nonapeptide systems in regulating complex social interactions like aggression and pair bonding.

Researchers generated vasopressin 1a receptor knockout (V1aR KO) prairie voles using CRISPR/Cas9-mediated genome editing. They compared the aggressive behavior of these V1aR KO males with oxytocin receptor knockout (OXTR KO) and wildtype (WT) males. Functional loss of V1aR was confirmed via 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. Primary endpoints also included partner preference and general social interaction.

Wildtype 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 stark contrast, both V1aR KO and OXTR KO males displayed a marked reduction in aggression toward male strangers. This reduction was significant, indicating a critical role for both receptor systems in mediating same-sex aggression. Notably, partner preference and social investigation behaviors were preserved in both knockout lines, suggesting a specific impact on aggression rather than general social deficits. > The functional loss of either V1aR or OXTR signaling genetically abolished same-sex conspecific aggression in male prairie voles without affecting their ability to form pair bonds.