The effect of chronic mild stress on tumor-bearing rats' behavior and its mechanism.

OBJECT: Much evidence has demonstrated that stress and tumor interact, but the mechanisms are poorly understood. The purpose of this study is to discuss the effect of unpredictable chronic mild stress (CMS) upon the behavior of Walker 256 tumor-bearing rats and its mechanism. METHODS: Observe the effects of CMS on the sucrose consumption, activities, body weight and levels of serums TNF-alpha and IL-6 of both tumor-bearing rats and non-tumor-bearing rats, and on the levels of Bcl-2 and the phosphor-ERK1/2 in their hippocampus. RESULTS: CMS can reduce the average sucrose consumption, behavioral scores, body weight gain, expression of Bcl-2 and p-ERK1/2 protein in hippocampus, and increase serums TNF-alpha and IL-6 of both tumor-bearing rats and non-tumor-bearing rats. The stressed tumor-bearing rats had less sucrose consumption, body weight gain and lower behavioral scores, but higher level of serum TNF-alpha than stressed non-tumor-bearing rats. A negative correlation was found between the levels of serum TNF-alpha and sucrose consumption, while a positive correlation between the expression of Bcl-2 protein in hippocampus proper and sucrose consumption. CONCLUSION: CMS can reduce the protein levels of Bcl-2 and p-ERK1/2 in the rats' hippocampus, which contributes to the changes in the rats' behavior caused by CMS. Tumor-bearing rats are prone to behave depressively after the exposure to CMS. Our findings have suggested that the tumor, by increasing the inflammatory reaction, can be taken as a stressor, affecting the hippocampus and consequently causing depression by decreasing the expression of Bcl-2 and p-ERK1/2 in hippocampus.

[Establishment of an rat model of tumor-associated depression].

OBJECTIVE: To establish an animal model of tumor-associated depression and observe their biological behaviors and biochemical indices. METHODS: Four groups of SD rats kept in separate cages were subjected to tumor cell inoculation with or without chronic unpredictable moderate stress administered before or after the inoculation. The depressive behaviors of the rats were examined by open-field test, and the concentration of 5-HT in the hippocampus was measured by spectrophotofluorometry. The body weight of the rats and volume of the implanted tumor were monitored and sugar water test was performed. RESULTS: The rats subjected to chronic stress displayed significant depression, manifested by reduction in movement in the central area and total movement distance with prolonged resting time and shortened time of activity. These rats maintained high levels of depression even 12 days after withdrawal of chronic stress. Compared with the control group, the depressive rats showed obviously reduced sugar water consumption and hippocampal 5-HT level. Tumors of different sizes were observed in all rats in the 4 groups. CONCLUSION: A rat model of tumor-associated depression is established, and the tumor-bearing rats exhibit obvious depressive behaviors and reduced level of neural substance (5-HT), which provides a good basis for studying the association of depression with tumorigenesis,progression and prognosis of tumor.