Antidepressant Effect Of Hypidone (YL-0919) And Its Mechanisms Of Neuroplasticity

Objective:To explore the antidepression effect and its mechanism of neuronal plasticity of YL-0919.Methods:The chronic stress model of rats was established by chronic unpredictable stress. Allthe rats of chronic stress were involved in the following detection experiments ofbehavioral indictors, to estimate the pharmacodynamic effect of antidepressant of YL-0919.For Golgi-cox-staining, pyramidal neurons of hippocampus were selected the spine lengthsand branch nodes appraise the modulation effect of YL-0919to the complexity ofpyramidal neurons. The normal rats were disposed by sub-chronic intragenicadministration for7days or chronic for21days of YL-0919. We detected LTP in thehippocampus of rats by the electrophysiological method to evaluate the function ofneuroplasticity effect of YL-0919and the characteristic of time course.Results:YL-0919（1.25-2.5mg/kg i.g,4w）intragenic administration to the rats which sufferedthe chronic unpredictable stress, it could reverse performance of depression and anxiety.YL-0919could help the rats improve the sucrose preference （P<0.05）,reverse theanhedonia induced by chronic unpredictable stress, significantly improve the reactivity ofrats that is suffered chronic stress in open field test（P<0.05）, significantly shorten theingestion latency period in the latency to feeding test（P<0.05）, increase the preference ofopen arm entry and open arm time expect influence the total arm entry and total arm time（P<0.05）. These test all indicate that YL-0919have clearly effect of antidepressant. Thestudy of Golgi staining demonstrated that not only YL-0919but also fluoxetine couldincrease the spine lengths and branch nodes of pyramidal neurons of hippocampus ofstressed rats. It point out YL-0919and fluoxetine had increase the complexity of pyramidal neurons and the protective effect on the neuron, could improvement of structuralneuroplasticity of stressed rats. In LTP study, YL-0919（1.25-5mg/kg, i.g,7d or21d）andfluoxetine（10mg/kg, i.g,21d） could significantly promote the increasing extent of the PSpeak and EPSP slope after high frequency stimulation（P＜0.05～0.001），it was indicatethat both of them could increase the function neuroplasticity effect of hippocampus.However, YL-0919has faster onset than fluoxetine.Conclusion:Our research showed that YL-0919has the excellent effects of antidepressant、cognitive-enhancer in rats induced by chronic unpredictable stress. The underlyingantidepressant mechanisms of YL-0919might be related that YL-0919increases thepyramidal neurons of hippocampus and structural neuroplasticity. YL-0919could increasethe functional neuroplasticity using the shorten time (7d), it is indicated that YL-0919hasfaster onset in the antidepressant effect than fluoxetine.