The potential role of Saiko-ka-ryukotsu-borei-to in mitigating the severity of anxiety induced by social defeat stress in mice.

Aim: Major depressive disorder is a growing global concern with limited treatment options. Social stress contributes to its development, yet pharmacological prevention and mitigation remain underexplored. This study examined the effects of Saiko-ka-ryukotsu-borei-to (SRBT) on depressive and anxiety-like behaviors in mice exposed to social defeat stress (SDS). Methods: C57BL/6J mice were subjected to daily 10-min interactions with larger, more aggressive ICR mice for 10 consecutive days to induce SDS. Immediately following each session, mice were orally administered SRBT, fluoxetine (Flu), or saline (Sal), and were assigned to the SD-SRBT, SD-Flu, and SD-Sal groups, respectively. Mice that received Sal without SDS exposure served as the normal control (NC) group. On the 11th day, behavioral assessments, including the elevated plus maze (EPM) test, tail suspension test (TST), and social interaction test (SIT), were conducted across the four groups. Plasma corticosterone levels were also measured. Results: SDS significantly increased anxiety-like behavior in the EPM, as shown by reduced open arm time in the SD-Sal and SD-Flu groups. This effect was less evident in the SD-SRBT group. Although the SD-Flu group showed similar anxiety-like behavior to the SD-Sal group, no significant difference in open arm time was observed. SDS did not induce social avoidance or depressive-like behavior in the SIT or TST, nor did it alter plasma corticosterone levels. Conclusion: This study suggested that SRBT has the potential to mitigate anxiety caused by social stress. However, further ongoing evaluation and investigation are required to assess the effectiveness of SRBT.