• oxytocin;
  • oxytocin receptor;
  • social recognition;
  • maternal nurturing;
  • CD38;
  • ADP-ribosyl cyclase;
  • autism

Oxytocin in the hypothalamus is the biological basis of social recognition, trust, love and bonding. Previously, we showed that CD38, a proliferation marker in leukaemia cells, plays an important role in the hypothalamus in the process of oxytocin release in adult mice. Disruption of Cd38 (Cd38−/−) elicited impairment of maternal behaviour and male social recognition in adult mice, similar to the behaviour observed in Oxt and oxytocin receptor (Oxtr) gene knockout (Oxt−/− and Oxtr−/−, respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalisation calls was lower in Cd38−/− than Cd38 +/+ pups. However, these behavioural changes were much milder than those observed in Oxt−/− and Oxtr−/− mice, indicating less impairment of social behaviour in Cd38−/− pups. These phenotypes appeared to be caused by the high plasma oxytocin levels during development from the neonatal period to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of plasma oxytocin differentiation. Breastfeeding was an important exogenous source of plasma oxytocin regulation before weaning as a result of the presence of oxytocin in milk and the dam’s mammary glands. The dissimilarity between Cd38−/− infant behaviour and those of Oxt−/− or Oxtr−/− mice can be explained partly by this exogenous source of oxytocin. These results suggest that secretion of oxytocin into the brain in a CD38-dependent manner may play an important role in the development of social behaviour.