Oxytocin and CD38 in the paraventricular nucleus play a critical role in paternal aggression in mice

• Published in: Hormones and behavior 2020-04, Vol.120, p.104695-104695, Article 104695
• Main Authors: Shabalova, Anna A., Liang, Mingkun, Zhong, Jing, Huang, Zhiqi, Tsuji, Chiharu, Shnayder, Natalia A., Lopatina, Olga, Salmina, Alla B., Okamoto, Hiroshi, Yamamoto, Yasuhiko, Zhong, Zeng-Guo, Yokoyama, Shigeru, Higashida, Haruhiro
• Format: Article
• Language: English
• Subjects: ADP-ribosyl Cyclase - metabolism; ADP-ribosyl Cyclase 1 - metabolism; Aggression - drug effects; Animals; Animals, Newborn; c-Fos; CD38; Fathers - psychology; Female; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Male; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred ICR; Mice, Knockout; Nesting Behavior - drug effects; Oxytocin; Oxytocin - pharmacology; Paraventricular Hypothalamic Nucleus - drug effects; Paraventricular Hypothalamic Nucleus - metabolism; Paraventricular nucleus; Parental behavior; Paternal aggression; Paternal Behavior - drug effects; Social Behavior
• ISSN: 0018-506X; 1095-6867
• DOI: 10.1016/j.yhbeh.2020.104695

In mammals, the development of healthy offspring requires maternal care. Behavior by lactating mothers toward other individuals is an important component of maternal aggression. However, it is unclear whether fathers display aggression primed by pups (an external factor), and the protection mechanism is poorly understood. To address this question, we examined paternal aggression in the ICR mouse strain. We found that sires exposed to cues from pups and lactating dams showed stronger aggression toward intruders than did sires that were deprived of family cues or exposed to nonlactating mates. c-Fos immunohistochemistry showed that cells in both the paraventricular and supraoptic nuclei (PVN and SON, respectively) in the hypothalamus of sires exposed to any cues were highly activated. However, c-Fos activation in oxytocinergic neurons was increased only in sires exposed to pup cues and solely in the PVN. In Cd38-knockout sires, the presence of pups induced no or reduced parental aggression; however, this phenotype was recovered, that is, aggression increased to the wild-type level, after intraperitoneal administration of oxytocin (OT). Specific c-Fos activation patterns induced by pup cues were not found in the PVN of knockout sires. These results demonstrate that the PVN is one of the primary hypothalamic areas involved in paternal aggression and suggest that a CD38-dependent OT mechanism in oxytocinergic neurons is critical for part of the behavior associated with the protection of offspring by nurturing male mice. •Sires of the ICR mouse strain display aggression to intruders.•Pup cues induce paternal aggression.•Pup cues increase oxytocinergic neurons' activation in the paraventricular nucleus.•CD38-knockout mice do not exhibit paternal aggression.•Oxytocin supplementation rescues aggression in CD38-knockout sires.