Trifoliate Orange Daisy Decoction Of Depression Model Mice Behavior And Its Mechanism

This study using depression model mice induced by multivariate chronic unpredictable stressors (foot shock, crowding, crowding+hot stimulation, cold water stimulation, water deprivation, food deprivation and all-night lighting, unexpectedly given to mice, one method each day in 21 days), and give the animal different doses of Chinese Medical prescription of Zhijujieyu-tang. Healthy Kunming mice were randomly divided into six groups:the control group, the model group, the positive control (fluoxetine) group, the low, medium and high concentration of Zhijujieyu-tang groups. We examined the spontaneous activity, emotional behavior change and spatial learning memory ability changes in mice by using Open-field,Tail-suspension and Morris water maze tests, and examined the changes of SOD activity and MDA content in hippocampus (HP) and prefrontal cortex (PFC). The changes of morphological structure in HP and PFC of mice brain were observed by HE dye. The expression of c-fos in HP and PFC of mice brain were examined using immunohistochemical method. This study aims to investigate the effects of chronic stress on the behavior in mice and the mechanism of Chinese Medical prescription of Zhijujieyu-tang.The results of this study are as follows:1. Compared with the control group mice, the square crossing, rearing and grooming of the model group mice were remarkably decreased, and the central cell residence time and defecation were significantly increased in model group mice. Compared with the model group mice, the behavior of Open-field test in the fluoxetine and medium concentration of Zhijujieyu-tang group mice existed remarkable difference, and the square crossing, rearing and the central cell residence time in the high concentration of Zhijujieyu-tang group mice existed significant variation.2. Compared with the control group mice, the latency immobility (first immobile time) and immobility time (latter 4 minutes immobile time) of Tail-suspension test were significantly increased in model group mice. Compared with the model group mice, the latency immobility and immobility time were remarkably decreased in fluoxetine group and medium concentration group mice, and the latency immobility were remarkably decreased in the low and high concentration group mice,3. Compared with the control group mice, the escape latency to find platform of the model group mice were markedly increased, and the resident time in target quadrant remarkable decreased in the model group mice. Compared with the model group mice, the escape latency to find platform of the fluoxetine, medium concentration group of Zhijujieyu-tang mice were remarkably decreased, and the resident time in target quadrant remarkable increased in the different medicinal dosages group mice, the medium concentration group of Zhijujieyu-tang mice was very remarkably.4. Compared with the control group mice, the SOD activity were significantly decreased, and MDA content were markedly increased in the brain tissue of model group mice. Compared with the model group mice, the SOD activity were markedly increased, and MDA content were significantly decreased in the different medicinal dosages group mice.5. In the control, fluoxetine, medium and high concentration groups mice of Zhijujieyu-tang, there are lots of neurons in CA1, CA3 areas and Dentate gyrus(DG) area of HP, they arrange tidily, administrative levels is compact. Cell nucleus was dyed deep colour, and located at the center of cells. The neurons in PFC have tidy shape, they arranged orderly, and they are dyed even. In low concentration group mice of Zhijujieyu-tang, the morphological results showed that cells arrange still less, and its number has decreased, they are dyed lightly. Their shape is untidy.In the model group mice of Zhijujieyu-tang, the nerve cell are irregular in shape, and arrange untidily and laxly in in HP and PFC. The layers decreased obviously. Some cells show putrescence, some swollen. They are dyed uneven.6. Compared with the control group mice, the number of c-fos positive cells in HP and PFC of the model group mice brain were remarkably decreased, and the average target gray value were significantly increased. Compared with the model group mice, the number of c-fos positive cells in HP and PFC of the medium, high concentration group mice of Zhijujieyu-tang were markedly increased, and the average target gray value were markedly decreased.Conclusions are as follows:1. Zhijujieyu-tang could markedly improve the changes of behavior induced by chronic stress in mice. It suggested that it have a certain effects of anti-depression.2. Zhijujieyu-tang could increase the SOD activity, and decrease MDA content in chronic stress induced-depression model mice brain. With the inhibition of lipid peroxidation and the scavenging of superoxide free radical, so that lighten damage of nerve cell, that may be the one of possible mechanisms of the anti-depression of Zhijujieyu-tang.3. Zhijujieyu-tang could resist the decrease of c-fos neurons in HP and PFC of depressive model mice brain, and reduce the damage of neuron in different areas of mice brain. The mechanism of antidepressant-like effects of Zhijujieyu-tan may be closely related to the up-regulation of c-fos expression in HP and PFC.