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

Abstract

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 OXT͞OXTR 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.lactation ͉ maternal behavior ͉ ultrasonic vocalization ͉ social discrimination ͉ aggressive behavior

Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice

“…76 Aggression is higher in male mice from OxtÀ/À mothers but the same, or possibly reduced, in male mice from heterozygous mothers. [77][78][79] In addition, female OxtÀ/À mice have more, and male mice less, anxiety-like behavior than Oxt þ / þ mice. 77,80 Therefore, it may be that the deficits seen in PCP-disrupted PPI in OxtÀ/À mice are an extension of their overall deficits in cognitive functioning, perhaps reflecting a change in the glutamatergic system, beyond the CSPP.…”

Advances in behavioral genetics: mouse models of autism

“…Other researchers have measured ultrasonic vocalizations in mouse pups separated from their mothers as a test for altered emotional behavior early in postnatal life (Table 1). [36][37][38][39][40][41][42][43][44][45][46] In most (but not all) of these studies, mouse pups with genetic alterations relevant to social behavior had decreased levels of ultrasonic vocalizations. These findings suggest that the vocalization assay may be useful to measure attenuated responses to social isolation in neonates.…”

Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population

“…14 OXTR knockout mice showed several aggravations in social behaviors including mother-offspring interaction. 16 In human, autistic children tended to have a lower plasma oxytocin level compared with healthy individuals. 17 Oxytocin infusion might reduce repetitive behaviors in autistic patients.…”