2005). However, the behavioral effects generally tend to be mild unless a susceptible strain of mouse is used, such as BALB/cJ (Wang et al.

2011). The MS model employed in this study has been widely used in rats, and produces consistent behavioral alterations (e.g., Boccia and Pedersen 2001; Daniels et al. 2004; O’mahony et al. 2009). A shorter, repeated version Inhibitors,research,lifescience,medical of the MS model commonly used in mice can be less reliable, sometimes eliciting changes but with no consistent effects (Millstein and Holmes 2007), possibly due to the dams ability to adapt and provide compensatory care to the pups (Franklin et al. 2010). As we used the single 24 h MS model, Inhibitors,research,lifescience,medical we did not expect to elicit such compensatory behavior in the dams but as we did not assess maternal care, we cannot exclude a potential impact of altered maternal behavior in our study. Our data find differences between MS and controls specifically in the home cage, open field and novel object exploration tests. As with previous findings (Eklund

and Arborelius 2006; Renard et al. 2007), we found the effects of the MS model to be sex-dependent, with Inhibitors,research,lifescience,medical stronger effects observed in males. It is interesting to note that the strongest phenotypic differences occur mostly in males, while in human samples the prevalence of mental disorders such as depression is higher in females. MS male mice from both strains displayed altered activity characterized Inhibitors,research,lifescience,medical by rapid bursts of locomotor activity over short distances

in Inhibitors,research,lifescience,medical the home cage and LEE011 concentration increased exploration of a novel arena. Increased exploration of a novel arena following early life stress has been reported previously in a number of studies (Daniels et al. 2009; Franklin et al. 2010) and has been suggested to be a result of hyperarousal or due to changes in stress reactivity. Conversely, DBA/2J female mice exposed to MS displayed reduced exploration of a novel arena, indicative of an anxiety-like behavior. Although DBA/2J males exposed to MS displayed increased exploration of a novel arena, they showed Linifanib (ABT-869) reduced exploration of novel objects, which suggests an altered response in threatening (novel arena) versus non-threatening (novel object) situations following MS. We identified significant, but modest, changes in DNA methylation at CpG units in the promoter regions of three genes (Avp, Nr4a1, Nr3c1) following exposure to early life stress. In the Avp promoter, DNA methylation was increased at a single CpG Unit following MS in both strains of mice, with a >10% increase in the C57BL/6J strain.