CIS resulted in changes in emotional‐like behavior in Hint1‐KO (from the trend for anxiolytic‐like behavior to the elevated anxiety‐related behavior) and HT mice (from the trend of anxiolytic‐like and antidepression‐like behaviors, to the elevated anxiety‐related behavior and increased depression‐like behavior), may through other underlying molecular mechanisms. Here, HINT1 is linked to major depressive disorder.