Objective

2

To explore the therapeutic effect and mechanism of Chaihu Yueju decoction on model rats induced by chronic unpredictable mild stress （CUMS）.

Method

2

The 60 SD rats were randomly divided into normal group， model group， Chaihu Yueju decoction low， medium and high-dose groups（0.3， 0.6， 1.2 g·kg

-1

） and fluoxetine hydrochloride group（0.2 mg·kg

-1

）， 10 for each group. The model rats was established by chronic unpredictable mild stress for 5 weeks， and then Chaihu Yueju decoction and fluoxetine hydrochloride were given to the corresponding treatment group by gavage for 3 weeks. In the last week of gavage， Morris water maze training and testing were conducted. After the last day of gavage， sugar water preference and other behavioral experiment were tested. The sugar water preference test was used to detect the degree of pleasure deficiency in rats before and after treatment， the open field test was used to detect the depression of rats before and after treatment， the spatial memory ability was tested by Morris water maze. Western blot was used to detect the levels of tumor necrosis factor-

α

（TNF-

α

）， 5-hydroxytryptamine receptor 1A （5-HT1A）， extracellular signal-regulated kinase （ERK） and synapse associated protein in hippocampus of each group， Gloji and Nissl staining was used to observe the changes of dendritic spines and Nissl bodies in the hippocampus CA3.

Result

2

Compared with normal group， the weight， sugar water preference rate， the scores of horizontal and vertical movement were significantly reduced （

P

<

0.05）， and the immobility time was significantly prolonged in model group （

P

<

0.05）. Meanwhile， the ability of learning and memory in model group decreased （

P

<

0.05）. Western blot results showed that the levels of TNF-

α

was significantly increased （

P

<

0.05）， and the levels of 5-HT1A， p-ERK， cyclic adenosine phosphate reactive element binding protein （CREB）， p-CREB， Synapsin-1，Synaptophysin， glutamate receptor subtype-1（GluR-1）and postsynaptic membrane protein-95（PSD-95） in model group were significantly decreased （

P

<

0.05）. Gloji and Nissl staining results showed that the density of dendritic spines and the number of Nissl body in the hippocampal CA3 of the model group was obviously attenuate （

P

<

0.05）. The results show that the neurons were evidently damaged. Compared with model group， the weight， sugar water preference rate， the scores of horizontal and vertical movement were clearly increased （

P

<

0.05） and the immobility time was significantly shortened in fluoxetine hydrochloride group， middle dose and high dose Chaihu Yueju decoction group （

P

<

0.05）. Western blot results showed that the levels of synaptophysin， GluR-1 and PSD-95 were significantly increased in fluoxetine hydrochloride group， middle dose and high dose Chaihu Yueju decoction group. The level of TNF-

α

was significantly decreased （

P

<

0.05）， the levels of 5-HT1A， p-ERK， CREB， p-CREB and Synapsin-1 were remarkably increased （

P

<

0.05）， especially the high dose group of Chaihu Yueju decoction. Gloji and Nissl staining results showed that the density of dendritic spines and the number of Nissl body in the hippocampal CA3 of high dose group were similarly increased in a dose-dependent manner.

Conclusion

2

Chaihu Yueju decoction could improves the weight， the depressive despair， autonomous activity ability and learning and memory ability of DP model rats. Its mechanism is closely related to attenuating the inflammatory reaction and enhancing the levels of 5-HT1A receptor protein， ERK and synapse related protein， then activating 5-HT/CREB and ERK/CREB signaling pathways， increasing the number and distribution of dendritic spines and repairing damaged neurons in the DP model rat's hippocampus.