Antidepressant effects of Kai-Xin-San in fluoxetine-resistant depression rats

This study aimed to investigate the antidepressant effect and the mechanism of action of Kai-Xin-San (KXS) in fluoxetine-resistant depressive (FRD) rats. Two hundred male Wistar rats weighing 200 +/- 10 g were exposed to chronic and unpredictable mild stresses (CUMS) for 4 weeks and given fluoxetine treatment simultaneously. The rats that did not show significant improvement in behavioral indexes were chosen as the FRD model rats. These rats were randomly divided into four groups: FRD model control; oral fluoxetine and aspirin; oral KXS at a dose of 338 mg . kg(-1) . day(-1); and oral KXS at a dose of 676 mg . kg(-1) . day(-1). Rats continued to be exposed to CUMS and underwen treatment once a day for 3 weeks, then cytokine (COX-2, IFN-gamma, IL-1 beta, IL-2, IL-4, IL-6, IL-10, TGF-beta, and TNF-alpha) levels in the hippocampus and serum, and organ coefficients were measure. Both doses of KXS improved the crossing and rearing frequencies, sucrose-preference index, and body weight in FRD rats. KXS at a dose of 338 mg . kg(-1) . day(-1) reduced COX-2, IL-2, IL-6, TNF-alpha levels, increased IL-10 level in the hippocampus, and reduced IL-2 and TNF-alpha levels in serum. KXS at a dose of 676 mg . kg(-1) . day(-1)reduced TNF-alpha level in the hippocampus, reduced IL-2 and TNF-alpha levels in serum, and increased IFN-gamma and IL-10 levels in the hippocampus and serum. There were no significant differences in organ-coefficients of the spleen among and between groups. The results suggested that oral administration of KXS in FRD rats was effective in improving behavior disorders by influencing various inflammatory pathways.