Effect Of Huazhuo Jiedu Shugan Recipe On The Behavior And The Expression Of TPH2,βCaMKⅡ And SERT In Depression Model Mice

Objective:To study the effect of Huazhuo Jiedu Shugan Recipe on behavioral changes and the TPH2,βCaMKⅡ and SERT expression in the chronic unpredictable mild stress（CUMS）model mice.Methods:48 ICR mice were fed for one week.After 1 week of adaptive feeding,the mice were randomly assigned to 6 experimental groups as follows:the normal group,the model group,the fluoxetine group and the low,medium and high dose group of Huazhuo Jiedu Shugan recipe（traditional Chinese medicine）.The depressive model was established by CUMS.The molding cycle was 21 days.During the modeling,all treatments were administered to the mice via gastric gavages.The normal group and the model group were intragastrically administered with a 15 m L·kg^-1 saline vehicle,the fluoxetine group was administered with the fluoride hydrochloride of 10mg·kg^-1,while the mice in the low,medium and high dose group(0.85g·kg^-1,1.7g·kg^-1,3.4g·kg^-1)of Huazhuo Jiedu Shugan recipe were given traditional Chinese medicine by gastric lavage.After the administration,the depression-like behaviors were analyzed in mice by the methods of sugar water preference test,forced-swimming test,tail suspension test,novelty-suppressed feeding test and open-field test.The expression of the TPH2,βCaMKⅡ and SERT were determined by immunohistochemistry.All data were analyzed using a one-way analysis of variance（ANOVA）.Results:1.Behavioral test results（1）The sugar preference score in the model group was significantly decreased compared with the normal group（P<0.01）;The sugar preference score in the fluoxetine group,the high dose and middle group of traditional Chinese medicine was significantly increased compared with the model group（P<0.01）.（2）The immobility time of forced-swimming test in the model group was significantly prolonged compared with the normal group（P<0.01）;The immobility time of forced-swimming test in the fluoxetine group,the high dose and middle group of traditional Chinese medicine was significantly shortened compared with the model group（P<0.05 or P<0.01）.The latency to immobility of forced-swimming test in the model group was significantly shortened compared with the normal group（P<0.01）;The latency to immobility of forced-swimming test in the fluoxetine group,the high dose and middle group of traditional Chinese medicine was prolonged compared with the model group（P<0.05 or P<0.01）.（3）The immobility time of tail suspension test in the model group was significantly prolonged compared with the normal group（P<0.01）;The immobility time of tail suspension test in the fluoxetine group,the low,medium and high dose group of traditional Chinese medicine was shortened compared with the model group（P<0.05 or P<0.01）.（4）The latency of novelty-suppressed feeding in the model group was significantly prolonged compared with the normal group（P<0.01）;The latency of novelty-suppressed feeding in the fluoxetine group,the low,medium and high dose group of traditional Chinese medicine was shortened compared with the model group（P<0.05 or P<0.01）.（5）The duration and the distance was shorted in the center,and the entries into the center was decreased in the model group compared with the normal group（all P<0.01）;The duration was prolonged,the distance was lengthened and the entries into the center was increased in the fluoxetine group,the low,medium and high dose group of traditional Chinese medicine compared with the model group（P<0.05 or P<0.01）.2.Immunohistochemistry test results（1）The expression of TPH2 in DRN of the model group was significantly reduced compared with the normal group（P<0.01）;The expression of TPH2in DRN of the fluoxetine group and the medium and high dose group of traditional Chinese medicine was significantly increased compared with the model group（P<0.01）.（2）The expression ofβCaMKⅡ in LHb and SERT in hippocampal CA3of the model group was significantly increased compared with the normal group（all P<0.01）;The expression ofβCaMKⅡ in LHb and SERT in hippocampal CA3 of the fluoxetine group and the medium and high dose group of traditional Chinese medicine was significantly decreased compared with the model group（all P<0.01）.Conclusion:1.The CUMS method can successfully induce such depression-like behaviors as anhedonia,behavioral despair and decreased exploratory desire in mice,and there is a high similarity between the behavior of depression model mice and the human beings’depressive behavior.2.Huazhuo Jiedu Shugan Recipe can improve effectively the depression-like behavior and cognition of the CUMS model mice.3.The anti-depression underlying mechanism of Huazhuo Jiedu Shugan Recipe may be related to the down-related expression ofβCaMKⅡ,SERT and the up-regulated expression of TPH2.