Locomotor activity, ultrasonic vocalization and oxytocin levels in infant CD38 knockout mice

Oxytocin (OT), a neurohormone involved in reproduction, plays a critical role in social behavior in a wide range of mammalian species from rodents to humans. The role of CD38 in regulating OT secretion for social behavior has been demonstrated in adult mice, but has not been examined in pups or during development. Separation from the dam induces stress in 7-day-old mouse pups. During such isolation, locomotor activity was higher in CD38 knockout (CD38^-/-) pups than in wild-type (CD38^+/+) or heterozygous (CD38^+/-) controls. The number of ultrasonic vocalizations was lower in CD38^-/- pups than in CD38^+/+ pups. However, the difference between the two genotypes was less severe than that in OT knockout or OT receptor knockout mice. To explain this, we measured plasma OT levels. The level was not lower in CD38^-/- pups during the period 1-3 weeks after birth, but was significantly reduced after weaning (>3 weeks). ADP-ribosyl cyclase activities in the hypothalamus and pituitary were markedly lower from 1 week after birth in CD38^-/- mice and were consistently lower thereafter to the adult stage (2 months old). These results showed that the reduced severity of behavioral abnormalities in CD38^-/- pups was due to partial compensation by the high level of plasma OT.