2009; Berardelli et al. 2013; Medina et al. 2013). Furthermore, human carriers of certain MR alleles are more reactive to stress, showing enhanced amygdala activation and HPA activation in response to stress (van Leeuwen et al. 2011; Bogdan et al. 2012). It should be noted that behavioral alterations between JS and control animals were only found in one measure of

anxiety behavior, the EPM, and not in two subsequent tests (open field and emergence test). A possible reason for this is that experience of the EPM (first test encountered) could have affected subsequent performance in the open field and emergence tests, and suggests caution when performing Inhibitors,research,lifescience,medical multiple behavioral tests on the same animal, something which remains an unresolved issue in behavioral test batteries (Paylor et al. 2006; Blokland et al. 2012). Alternatively, it has been suggested that these three tests Inhibitors,research,lifescience,medical measure subtly different aspects of anxiety-like behavior (Ramos 2008), with the current results suggesting a selective deficit on the EPM. A further option is that stress effects on anxiety are subtle, Inhibitors,research,lifescience,medical with effects seen in only one out of the three tests performed. Sex differences Sex differences were found in all three

behavioral tests performed, with female animals displaying lower levels of anxiety-like behavior and greater levels of activity. Female mice Inhibitors,research,lifescience,medical and rats typically display less anxiety than males in the EPM (Zimmerberg and Farley 1993; Voikar et al. 2001). In the present study, we find that hippocampal GR expression is higher in females, suggesting a role for CRs in differences in anxiety behavior between the

sexes. This result adds to recent findings of sex differences in forebrain GR (including hippocampus) on HPA axis Trametinib nmr regulation and Inhibitors,research,lifescience,medical depression-type behaviors (Solomon et al. 2012). As sex differences are found in the development of neuropsychiatric disorders (Bao and Swaab 2010), this highlights further that males and females need to be considered separately in basic research models, and suggests different MR/GR the between sexes may contribute to sex differences in vulnerability to stress-related disorders. Conclusion Experiencing stress in the prepubertal or juvenile phase increased anxiety-like behavior and altered the expression of MR and GR:MR in the hippocampus in adulthood. This alteration in CR expression provides a potential mechanism for the observed increase in anxiety-like behavior observed in adulthood. Further evidence for the involvement of CR receptors in adult anxiety-like behavior is provided by the finding that females demonstrated greater GR and GR:MR expression in the hippocampus, with corresponding decreases in anxiety-type behaviors when compared to males.