Effects of Early Proinflammatory Stress on Anxiety and Depression-Like Behavior in Rats of Different Ages

Abstract

Early proinflammatory stress created by administration of lipopolysaccharide (LPS) (50 μg/kg s.c.) on days 3 and 5 of postnatal life led to decreases in movement activity, reductions in exploratory behavior, and increases in anxiety in rats at adolescent age (1–1.5 months) in the open field and elevated plus maze tests. Greater changes in anxiety behavior were seen in males than females. Administration of LPS in early ontogeny induced signs of depression-like behavior at adolescent age in both males and females, this being detected in the anhedonia test as a reduction in the preference for 1% sucrose solution, unlike the situation in the control groups. The forced swimming test showed signs of depression-like behavior in males but not in females, but only on first testing. In adult rats (3–3.5 months), after increased handling and acquisition of food-procuring reflexes, these changes in anxiety and depression-like behavior largely disappeared. Administration of LPS at early age led to increased serum IL-1β levels in adult males after repeated stress exposure, while females showed increased corticosterone levels as compared with control animals. These results provide evidence of increased signs of anxious-depressive behavior in rats after early exposure to proinflammatory stress, along with sex-related differences and the possibility of correcting the negative consequences of stress in later life.