Abstract:Objective：To explore the antidepressant effect of the total flavonoids extracted from cottonseed (CTN-T) and its possible mechanism.Methods：The learned helplessness model in rats was used to evaluate the antidepressant effect of CTN-T. Using the 5-hydroxytryptophan（5-HTP）induced head twitch response test and yohimbine toxicity potentiation test in mice，the possible monoamine targets of the antidepressant action of CTN-T were detected. Moreover， high performance liquid chromatography and electrochemical detection (HPLC-ECD) was used to determine the content of monoamine and metabolites in the hippocampus of rats following CTN-T administration.Results：Repeated administration of CTN-T (50，100 mg·kg^-1，ig，twiceper day for 4 d) significantly decreased the helplessness behavior induced by inescapable foot- shock in learned helplessness test in rats. Repeated administration of CTN-T (50，75 mg·kg^-1， ig，twice per day for 4 d) significantly increased the 5-HTP induced head twitch response in mice，while CTN-T (60 mg·kg^-1，ig，twice per day for 4 d) had a tendency to potentiate yohimbine toxicity in mice. Repeated administration of CTN-T (25~75 mg·kg^-1，ig，twice per day for 4 d)，the neurochemical assays showed that the content of 5-hydroxytryptamine (5-HT) was increased in rat hippocampus at 25 and 100 mg·kg^-1dose of CTN-T，and that the content of norepinephrine (NE) was increased at 50 and 100 mg·kg^-1dose of CTN-T. By contrast，CTN-T had no effects on the content of dopamine (DA)，epinephrine (E)，5-hydroxyindolacetic acid (5-HIAA) and the rate of 5-HT/5-HIAA.Conclusion：CTN-T exerts antidepressant effects which may be closely related to the strengthening of the hippocampal serotonergic and noradrenergic function.

Key words:depression,totalflavonoids extracted from cottonseed（CTN-T）,learnedhelplessness model,5-hydroxytryptamine（5-HT）,norepinephrine（NE）