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

Oct 27, 2005Proceedings of the National Academy of Sciences of the United States of America

Widespread social problems but normal birth behavior in mice lacking oxytocin receptors

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Abstract

Oxtr(-/-) mice exhibited normal parturition but had defects in lactation and maternal nurturing.

Oxtr(-/-) mice did not show obvious deficits in fertility or reproductive behavior.
Infant Oxtr(-/-) males emitted fewer ultrasonic vocalizations in response to social isolation compared to wild-type littermates.
Adult Oxtr(-/-) males displayed deficits in social discrimination and increased aggressive behavior.
Aggression levels were high in Oxt(-/-) males raised by Oxt(-/-) dams, but not in those raised by Oxt(+/-) dams.
The data indicate a potential developmental role of the OXT/OXTR system in influencing adult aggressive behavior.

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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.

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

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