Preventive effect of a Kampo medicine, kososan, on recurrent depression in a mouse model of repeated social defeat stress

• Published in: Gene Vol. 806; p. 145920
• Main Authors: Ito, Naoki, Sasaki, Kazunori, Hirose, Eiji, Nagai, Takayuki, Isoda, Hiroko, Odaguchi, Hiroshi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 05.01.2022
• Subjects: Antidepressant; Kososan; Recurrent depression; Social defeat stress; Antidepressant; Social defeat stress; Tnnt1; SDS; Kososan; Recurrent depression; SAT; GO; DAVID; Enpp2; IFN-α; Homer1; Ttr; ANOVA; SI; Zic1; KEGG; mRSDS; Scai
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2021.145920

•Stress-experienced mice recurred depression by re-exposure of single stress.•Kososan, but not milnacipran, prevented the recurrent depression in mice.•We found several genes which could be implied in the preventive effect of kososan.•We first propose a beneficial effect of kososan on recurrent depression. 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.