Abstract

Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice.

Highlights

  • Stress experienced early in life may cause persisting changes in stress responsiveness, emotionality and cognitive performance, and increase the risk to develop psychopathologies, such as major depression, anxiety or personality disorders, later in life (De Bellis and Thomas, 2003; Cicchetti and Toth, 2005; Yasik et al, 2007; Green et al, 2010; Tottenham et al, 2010; Pechtel and Pizzagalli, 2011)

  • Since we hypothesized that mineralocorticoid receptor (MR) overexpression would moderate the effects of Early-life stress (ELS), we were interested in interaction effects of the two factors

  • The aim of this study was to determine whether—in female mice—the effects of ELS on anxiety and memory formation is moderated by transgenic overexpression of MRs

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Summary

Introduction

Stress experienced early in life may cause persisting changes in stress responsiveness, emotionality and cognitive performance, and increase the risk to develop psychopathologies, such as major depression, anxiety or personality disorders, later in life (De Bellis and Thomas, 2003; Cicchetti and Toth, 2005; Yasik et al, 2007; Green et al, 2010; Tottenham et al, 2010; Pechtel and Pizzagalli, 2011). Women are at higher risk of developing affective and cognitive disturbances under adverse life conditions than men (Lewinsohn et al, 1998; Kessler, 2003; Steiner et al, 2003; Wittchen and Jacobi, 2005; Bekker and van Mens-Verhulst, 2007). In a large population sample of aged individuals (men and women), polymorphisms of NR3C2 encoding MR

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