Developmental effects of early immune stress on aggressive, socially reactive, and inhibited behaviors

The origins of individual differences in social development are examined in relation to early stress (immune challenge) and social milieu (maternal be havior) in a genetic-developmental analysis using an animal model. Neonatal mate mice (5 or 6 days of age) from two lines of mice selectively bred for high versus low levels of intermale aggressive behavior received a standar d immune challenge (i.p. injections of 0.05 mg/kg endotoxin or saline). Ani mals were reared by their line-specific biological dam or by a foster dam f rom a line bred without selection. Adult levels of social behaviors were as sessed in a dyadic test (age 45-50 days). Mice from the high-aggressive lin e show more developmental sensitivity to immune challenge than mice from th e low-aggressive line, and line differences persist regardless of the early maternal environment. As adults, endotoxin-treated mice from the high-aggr essive line have lower levels of aggressive behavior, longer latency to att ack, and higher rates of socially reactive and inhibited behaviors compared to saline controls. Developmental effects of endotoxin in the low-aggressi ve line are minimal: endotoxin increases socially reactive behaviors, compa red to saline controls, but only for mice reared by their biological dams. Rearing by foster dams increases social exploration in the low-aggressive l ine. The findings raise novel questions regarding the openness of behaviora l systems to effects of nonobvious but omnipresent features of the environm ent, such as antigenic load, how these effects are integrated to affect soc ial development and psychopathology, and the nature of intrinsic factors th at contribute to individual differences in sensitivity to early stressors.