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 behavior) in a genetic-developmental analysis using an animal model. Neonatal male mice (5 or 6 days of age) from two lines of mice selectively bred for high versus low levels of inter-male aggressive behavior received a standard immune challenge (i.p. injections of 0.05 mg/kg endotoxin or saline). Animals were reared by their line-specific biological dam or by a foster dam from a line bred without selection. Adult levels of social behaviors were assessed in a dyadic test (age 45-50 days). Mice from the high-aggressive line show more developmental sensitivity to immune challenge than mice from the low-aggressive line, and line differences persist regardless of the early maternal environment. As adults, endotoxin-treated mice from the high-aggressive line have lower levels of aggressive behavior, longer latency to attack, and higher rates of socially reactive and inhibited behaviors compared to saline controls. Developmental effects of endotoxin in the low-aggressive line are minimal: endotoxin increases socially reactive behaviors, compared to saline controls, but only for mice reared by their biological dams. Rearing by foster dams increases social exploration in the low-aggressive line. The findings raise novel questions regarding the openness of behavioral systems to effects of nonobvious but omnipresent features of the environment, such as antigenic load, how these effects are integrated to affect social development and psychopathology, and the nature of intrinsic factors that contribute to individual differences in sensitivity to early stressors.