Chronic social stress during early development is involved in antisocial maltreatment behavior in mice

Abstract

Purpose Early-life stress can cause brain inflammation and affect social behavior in adulthood. In humans, maltreated (abused or neglected) children often exhibit antisocial behavior, including violent and sadistic behavior, in adulthood. However, it is unknown whether maltreatment behavior occurs in rodents. Here, we developed an assay system to evaluate conspecific maltreatment behavior in the mouse. Methods To assess maltreatment behavior, we devised a two-chamber apparatus separated by a transparent partition, in which one chamber was provided with a nose-poking hole that would trigger foot shocks onto the other. Lidocaine was used to inhibit neural activity in vivo. Brain oscillations were investigated by electroencephalograph. Enzyme-linked immunosorbent assay was used for protein assay. The mouse model was sequentially subjected to maternal separation (MS), social defeat (SD), and social isolation (SI) in that order (MS/SD/SI model). Results Inactivation of the anterior cingulate cortex and medial prefrontal cortex increased the level of nose-poking. Maltreatment behavior provoked changes in oxytocin, corticosterone, and brain-derived neurotrophic factor levels. MS/SD/SI mice exhibited more sustained nose-poking behavior during the experiment, resulting in increased foot shocks to the mouse in the opposite chamber. Abnormal brain oscillations were observed in the MS/SD/SI mice. Conclusion The MS/SD/SI model and maltreatment-behavior assay may be useful not only to study the relationship between social stress in childhood and antisocial behavior in adulthood, but also for study of etiology, pathology, or treatment for brain disorders, such as psychopathy.