Abstract:Objective: To investigate the effects of different doses (50，25，12.5 mg·kg-1) of Proanthocyanidin (OPC) combined with piperine (5 mg·kg-1) on depression-like behaviors in mice under chronic unpredictable mild stress.Methods: Chronic stress was applied for 21 days. After that, the immobility time of mice in the forced swimming test and tail suspension test were observed respectively. In addition, the HPLC-ECD was used to analyze the concentration of monoamines and their metabolites in the hippocampus and frontal cortex, and Fluorescence spectrophotometry was used to analyze the monoamine oxidase activity in mice brain.Results: Compared with the control group，the stressed group decreased the immobility time in the forced swimming test and tail suspension test ; At the same time, reduced 5-HT and NE levels, but increased the ratio of 5-HIAA/5-HT in the hippocampus and frontal cortex of mice were observed. The OPC (50，25，12.5 mg·kg-1) combined with piperine (5 mg·kg-1) showed a significantly larger effect on these measures. In addition, MAO-A activity in the brain was increased significantly when the mice were exposed to chronic stress, but MAO-B activity was not changed. The combination strategy could significantly decrease MAO-A activity which was raised by chronic stress, while they did not affect the MAO-B activity.Conclusion: Proanthocyanidins in combination with piperine ameliorated depression-like behaviors induced by chronic unpredictable mild stress in mice, which may be partially mediated through the serotonin and noradrenaline systems.

Key words:proanthocyanidins,depression,piperine,combination