Depression is deemed a mood disorder characterized by a high rate of relapse. Therefore, overcoming of the recurrent depression is globally expecting. Kososan, a traditional Japanese herbal medicine, has been clinically used for mild depressive mood, and our previous studies have shown some evidence for its antidepressive-like efficacy in experimental animal models of depression. However, it remains unclear whether kososan has beneficial effects on recurrent depression. Here, we examined its effect using a mouse model of modified repeated social defeat stress (SDS) paradigm. Male BALB/c mice were exposed to a 5-min SDS from unfamiliar aggressive CD-1 mice for 5 days. Kososan extract (1.0 kg/kg/day) or an antidepressant milnacipran (60 mg/kg/day) was administered orally for 26 days (days 7–32) to depression-like mice with social avoidant behaviors on day 6. Single 5 min of SDS was subjected to mice recovered from the social avoidance on day 31, and then the recurrence of depression-like behaviors was evaluated on day 32. Hippocampal gene expression patterns were also assayed by DNA microarray analysis. Water- or milnacipran-administered mice resulted in a recurrence of depression-like behaviors by re-exposure of single SDS, whereas kososan-administered mice did not recur depression-like behaviors. Distinct gene expression patterns were also found for treating kososan and milnacipran. Collectively, this finding suggests that kososan exerts a preventive effect on recurrent depression-like behaviors in mice. Pretreatment of kososan is more useful for recurrent depression than that of milnacipran.

抑郁症被认为是一种以高复发率为特征的情绪障碍。因此，克服反复出现的萧条是全球所期待的。Kososan 是一种传统的日本草药，已在临床上用于轻度抑郁情绪，我们之前的研究已经在抑郁症的实验动物模型中显示了其抗抑郁样功效的一些证据。然而，尚不清楚kososan是否对复发性抑郁症有有益作用。在这里，我们使用修改后的重复社会失败压力 (SDS) 范式的小鼠模型检查了其效果。雄性 BALB/c 小鼠暴露于来自不熟悉的侵略性 CD-1 小鼠的 5 分钟 SDS 5 天。Kososan 提取物 (1。0 公斤/公斤/天）或抗抑郁药米那普仑（60 毫克/公斤/天）口服给药 26 天（第 7-32 天）给第 6 天出现社交回避行为的抑郁样小鼠。单次 5 分钟的 SDS 是在第 31 天接受从社交回避中恢复的小鼠，然后在第 32 天评估抑郁样行为的复发。还通过 DNA 微阵列分析测定了海马基因表达模式。水或米那普仑给药的小鼠通过再次暴露单一 SDS 导致抑郁样行为的复发，而 kososan 给药的小鼠没有复发抑郁样行为。还发现了用于治疗 kososan 和米那普仑的不同基因表达模式。总的来说，这一发现表明 kososan 对小鼠反复出现的抑郁样行为具有预防作用。