Impacts of early intervention with fluoxetine following early neonatal immune activation on depression-like behaviors and body weight in mice

Abstract

Several reports have suggested that early neonatal immune activation adversely influences the hypothalamic-pituitary-adrenal (HPA) axis development in humans and animal models. In addition, there have been several studies indicating that early intervention with fluoxetine (FLX) can alter HPA axis development and function, and prevent occurrence of behavioral abnormalities induced by common early-life insults. The present study aims to investigate the effects of early intervention with FLX following early neonatal immune activation on depression-like behaviors and body weight in mice. Neonatal mice in their postnatal days (PNDs) 3 and 5 received either lipopolysaccharide (LPS; 50 μg/kg, s.c.) or saline treatment, then male and female mice of both neonatal intervention groups received oral administration of FLX (5 and 10 mg/kg/day) or water via regular drinking bottles during the periadolescent period (PNDs 35-65). The results showed that neonatal LPS exposure elevated depression-like behaviors accompanied by increasing corticosterone levels in adulthood and decreasing body weight during neonatal and adolescent periods. Furthermore, the periadolescent FLX treatment inhibited the depression-like behaviors induced by neonatal infection in both sexes. This study obtained some experimental evidence indicating the potential adverse impacts of the FLX on normal behavioral development in male control animals. In conclusion, our findings suggest that an early pharmacological intervention with FLX may prevent emergence of depression-like behaviors induced by neonatal immune challenge without any detrimental effect on health in a sex- and dose-dependent manner in mice.