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The present study was undertaken to investigate the antidepressant potential of total alkaloids isolated from Semen Zizyphi Sponosae (TAS) and its possible mechanisms Mouse models of depression including the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate the effects of TAS. A possible mechanism was explored in the test of antagonism of reserpine-induced hypothermia in mice. Administration of 5, 10 and 20mg/kg (p.o.) TAS for 14 days significantly reduced the immobility time compared with the control group in the TST and FST in mice. The results also showed that the anti-immobility activity of SZS in these two tests is dose-dependent, without accompanying significant effects on locomotor activity. Furthermore, the mice were monitored body temperature after given reserpine (2.0mg/kg, i.p.)1 hour. The groups of SZS could remarkably inhibit the decrease of hypothermia in RRT at 1st hour. Therefore, these results suggest that SZS may be a component of the response to antidepressants, supporting a possible role for accommodating monoamine neurotransmitter in the symptoms of depression and the treatment of this condition.