Aim YL0919 is permitted by SFDA for clinical trial recendy as a new drug for depression.Whether YL0919 is a fastonset antidepressant and the possible mechanism related to mTOR pathway will be investigated.Methods Chronic unpredictable stress rat model was used to evaluate the fastonset effect of YL0919 through sucrose preference test and a series behavior test.Morphological, eletrophysiological and biochemical methods were used for measure the neurogenesis, synaptogenesis, LTP and molecules proteins related in mTOR pathways.Resuits YL0919 (i.g.for 5 d or 14 d) played faster onset effects of anxiolytic and antidepressant on novelty suppressed food test compared with fluoxetine.Repeated i.g YL0919 or fluoxetine (7d) increase the hippocampal LTP, Fluoxetine showed the same effect at the 21day in living rats in vivo.Chronic YL0919 treatment facilitated LTP in the hippocampus synapses more than fluoxetine treatment.Morphometric measurement and analysis showed that chronic YL0919 administration decreased the length of the active zone and reduced the thickness of CA1 postsynaptic densities compared to the normal, but were elevated compared to the fluoxetine group.Furthermore, the expression of hippocampal synaptogenesis was increased with chronic YL0919 administration but reduced with chronic fluoxetine treatment.Chronic administration (5 days) of YL0919 resulted in a significant antidepressant effect.The behavioral effects were associated with increases in hippocampal brainderived neurotrophic factor, synapsin,and mammalian target of rapamycin.Interestingly, the specific inhibitor of mTOR rapamycin can reverse the fastonset antidepressant effect of YL0919 on SPT, TST and FST and even in the protein expression.Conclusion These findings are the first time to supply evidence for fastonset antidepressant effect of YL0919.Furthermore,these effects appear to be associated with increases in markers of hippocampal neurogenesis, synaptogenesis and even mTOR protein expression, suggesting the mTOR pathway involving with the fastonset of YL0919.