Juvenile stress enhances anxiety and alters corticosteroid receptor expression in adulthood

Background: Exposure to stress in early life is correlated with the development of anxiety disorders in adulthood. The underlying mechanisms are not fully understood, but an imbalance in corticosteroid receptor (CR) expression in the limbic system, particularly the hippocampus, has been implicated in the etiology of anxiety disorders. However, little is known about how prepubertal stress in the so called juvenile period might alter the expression of these receptors. Aims: Therefore, the aim of this study was to investigate how stress experienced in the juvenile phase of life altered hippocampal expression of CRs and anxiety behaviors in adulthood. Materials and methods: We used a rodent model to assess the effects of juvenile stress on hippocampal CR expression, and performance in three behavioral tests of anxiety in adulthood. Results: Juvenile stress (JS) increased anxiety-like behavior on the elevated plus maze, increased mineralocorticoid receptor (MR) expression, and decreased the ratio of glucocorticoid receptor (GR) to MR expression in the hippocampus of adult animals. Females demonstrated lower levels of anxiety-type behavior and increased activity in three behavioral tests, and had greater expression of GR and GR: MR ratio than males, regardless of treatment. Discussion and conclusion: These results demonstrate that JS can alter the expression and balance of CRs, providing a potential mechanism for the corresponding increase in anxiety behavior observed in adulthood. Further evidence for the role of CR expression in anxiety is provided by sex differences in anxiety behavior and corresponding alterations in CR expression.