Effects of Sini San used alone and in combination with fluoxetine on central and peripheral 5-HT levels in a rat model of depression.

Objective: To investigate the effects of Sini San and fluoxetine on the levels of central and peripheral 5-HT in a rat model of depression, and provide new insight into the treatment of depression with integrated Chinese-Western Medicine.

Methods: A rat model of depression was established by chronic mild stress (CMS). Model rats received either Sini San, fluoxetine, a combination of the two drugs, or no drug treatment. Healthy naive rats were used as controls. Open field and sucrose preference tests were used to assess depression-like behavior. ELISA and immunohistochemistry were used to determine central and peripheral levels of 5-HT.

Results: In the group with no drug treatment, central 5-HT expression decreased while peripheral 5-HT concentrations increased as CMS continued. Four weeks after CMS, Sini San alone was less effective in reducing depression-like behavior than fluoxetine alone or in combination with Sini San, but combined use was more effective than fluoxetine alone. Eight weeks after CMS, Sini San alone or in combination with fluoxetine was more effective in reducing depression-like behavior than fluoxetine alone. Furthermore Sini San and fluoxetine used alone or in combination notably increased central 5-HT expression and decreased peripheral 5-HT levels in the rat model.

Conclusion: The results of the present study indicate that there is a synergistic action between the two medicines in the treatment of depression. Sini San exhibited a relatively long lag before its effects were observed; however, by eight weeks the Traditional Chinese Medicine appeared at least as effective as fluoxetine. We suggest that Sini San can replace fluoxetine in the later stages of depression treatment to minimize side effects observed with long-term fluoxetine administration.