Stressed BALB mice showed significantly longer latency periods to feeding (Figure S2F), with no significant differences in weight p38 MAP Kinase pathway loss induced by food deprivation (Figure S2G) or feeding activities (Figure S2H). Furthermore, the increased latency to feed induced by CUMS was reversed with continuous IMI treatment (Figure S2F). Anxiety behavior was also examined using the elevated zero
maze test. The amount of time spent in the open section and frequency of rearing were not affected by CUMS (data not shown). Social interaction time also provides an index of anxiety and depression-like behavior. More anxious and depressed rodents spend less time in social interactions (File and Seth, 2003 and Berton et al., 2006). PFT�� research buy Stressed BALB mice spent significantly less time engaged in social interactions and had fewer interactions than the nonstressed controls. This effect was also reversed with continuous IMI treatment (Figures S2I and S2J).
Taken together, these results indicate an increase in depression- and anxiety-related behaviors in stressed BALB mice. In contrast with the BALB mice, B6 mice subjected to CUMS did not show any behavioral changes in the sucrose preference test (Figures S3A and S3B) or forced swim test (Figures S3C and S3D), but they did demonstrate a reduced latency to feed in the novelty-suppressed feeding test (Figure S3E) and increased interaction times in the social interaction test
(Figure S3G), suggesting a decrease in anxiety-related behaviors in stressed B6 mice. In addition to behavioral characterization, we also examined the plasma corticosterone (CORT) levels of mice to investigate how CUMS influences neuroendocrine function. We found increased plasma CORT levels 60 min after the initiation of a stressor in both BALB and B6 mice on day 3 of the CUMS session (Figures S4A and S4B). In contrast, on day 38 of the CUMS session, B6 mice showed a reduction in plasma CORT levels 60 min below after the initiation of the stressor (Figure S4B). This effect was not observed in BALB mice (Figure S4A). Thus, BALB mice responded to CUMS with an increase in depression-like phenotypes, whereas the B6 mice responded to the same stress conditions with a decrease in anxiety-related behaviors. These behavioral and neuroendocrine data indicate that BALB and B6 mice develop “passive” and “active” responses to stress, suggesting that these strains of mice are susceptible and adaptive strains to CUMS, respectively. Neurotrophic factors play important roles in the regulation of synaptic and structural plasticity in the brain and may be involved in depression (Nestler et al., 2002 and Duman and Monteggia, 2006).