Abstract: Chronic stress may induce depression, but the mechanism is unclear. Previous studies suggested that dopamine system, especially dopamine receptor D2 (DRD2) may be involved in, and prostate apoptosis response-4 (par-4) may be the link point between DRD2 and depression. The aims of this research are to detect the expression of par-4 in striatum of a rat model of depression induced by chronic stress, and to explore whether DNA methylaion is involved in the regulatory mechanism of par-4 expression.
Newborn rats were randomly divided into two groups, when they grew up to ten weeks, the experimental group rats (n = 17) accepted chronic mild stress for 3 weeks, while the control group rats (n = 17) received no experimental handle. Their depressive level was assessed with forced swimming test and sucrose consumption test; the mRNA expression of par-4 and DRD2 in rats’ striatum was detected by Real-Time PCR; the protein expression of par-4 was detected by western blot; and the DNA methylation level of par-4 was investigated by bisulfated DNA sequencing.
The result showed that the float time of experimental rats was longer than the control rats (t = 4.01, p < 0.05), and the sucrose preference rate of experimental rats was reduced compare with the control rats (t = -2.93, p < 0.05). The par-4 and DRD2 mRNA expression of experimental rats were lower than the control rats (t values were -3.56 and -2.507 respectively, p < 0.05), and the fold changes of par-4 and DRD2 mRNA expression in experimental rats compared to control rats were 0.33 and 0.33 respectively. The par-4 protein expression of experimental rats was decreased compared with the control rats (t = -4.92, p < 0.05). However, there was no significant difference between two groups in methylation level of par-4 promoter region (t = -0.26, p > 0.05).
These results suggest that chronic mild stress could induce the depressive behaviors of rats and suppress the expression of par-4, but DNA methylation seems to be not involved in the regulatory mechanism.

Key words: Chronic mild stress, Depressive behaviors, Striatum, Prostate apoptosis response-4, Methylation