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CMS rats showed a significant decrease of superoxide dismutase, and a marked increase malondialdehyde levels in prefrontal cortex (PFC). We also found the CMS rats had elevated expression of HINT1, decreased levels of phosphorylated-PKC ε and aldehyde dehydrogenase-two (ALDH-2), and accumulated 4-hydroxynonenal (4HNE) in PFC. Moreover, CMS increased the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 in PFC. The alterations in behavior and molecule were prevented by antidepressant venlafaxine. These results demonstrat