Neonatal stress modulates sickness behavior.

The quality of the early environment, especially during the neonatal period, influences the development of individual differences in resistance to stress and illness in adulthood. A previous study demonstrated that neonatal stress augmented proinflammatory cytokine expression and viral replication in influenza virus-infected adult mice. The goal of the following study was to examine the lifelong effects of neonatal stress on the behavioral response to an immune challenge. Neonatal stress consisted of separating mouse pups from their dams (maternal separation, MSP) at critical points of their development. In the first study, pups were separated from the dam daily for 6h between postnatal day 1 and 14. As adults, these mice were infected with influenza A/PR8 virus. In a second study, a similar paradigm of MSP was employed, and as adults mice were injected with lipopolysaccharide (LPS) (ip). In a third study pups were separated from the dam for 24h on postnatal day 4 or 9. As adults, these mice received ip injections of LPS. In all three studies, changes in body weight, food and sweet solution consumption were examined following immune challenge. As previously described, activation of the immune system using influenza virus infection or LPS administration resulted in sickness behavior that consisted of body weight loss, anorexia and reduced consumption of a sweet solution. Furthermore, neonatal stress induced more rapid kinetics of sickness behavior and augmented several aspects of these symptoms. Together with previous studies, these findings suggest that neonatal stress disrupted the regulation of innate resistance to an immune challenge resulting in enhanced immunological and behavioral responses to immune activation. Thus, long lasting effects of early stress events may be the basis for individual differences in health and susceptibility to disease.