The oxytocin receptor (OXTR) and its ligand, oxytocin (OXT), regulate reproductive physiology (i.e., parturition and lactation) and sociosexual behaviors. To define the essential functions of OXTR, we generated mice with a null mutation in the Oxtr gene ( Oxtr -/- ) and compared them with OXT-deficient ( Oxt -/- ) mice. Oxtr -/- mice were viable and had no obvious deficits in fertility or reproductive behavior. Oxtr -/- dams exhibited normal parturition but demonstrated defects in lactation and maternal nurturing. Infant Oxtr -/- males emitted fewer ultrasonic vocalizations than wild-type littermates in response to social isolation. Adult Oxtr -/- males also showed deficits in social discrimination and elevated aggressive behavior. Ligand Oxt -/- males from Oxt -/- dams, but not from Oxt +/- dams, showed similar high levels of aggression. These data suggest a developmental role for the OXT/OXTR system in shaping adult aggressive behavior. Our studies demonstrate that OXTR plays a critical role in regulating several aspects of social behavior and may have important implications for developmental psychiatric disorders characterized by deficits in social behavior.

Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice