Impaired Cognitive Flexibility and Working Memory Precedes Depression: A Rat Model to Study Depression

Introduction: Depressive disorders are the 4th leading cause of health problems and the 2nd leading cause of burden among all diseases. Almost all depressive disorder patients have cognitive impairments to a certain extend. Studies about cognitive impairments in depression had been conducted, but whether cognitive dysfunctions are the cause or the effect is still not clear. Objectives: To analyze the process of working memory and cognitive flexibility impairments in a rat model of depression. Methods: In this experimental study, chronic unpredictable mild stress (CUMS) was used as a model of depression in 30 rats (Rattus novergicus). Cognitive function was assessed with the Morris water maze and attentional set shifting test. Results: This study found a significant difference on day 21 in working memory (p = 0.002) and cognitive flexibility (p = 0.036), which continued to day 41 in working memory (p = 0.001) and cognitive flexibility (p = 0.020). In the CUMS model of depression, parameters peak on day 41 and reveal parameter changes in weight gain (p = 0.018), food intake (p < 0.001), changes in food intake (p = 0.001), and the sucrose preference (p = 0.005), elevated plus maze (p = 0.001), and light dark box tests (p = 0.020). Conclusion: In a rat model of depression, cognitive impairment preceded depression, but it might be caused by anxiety-like behavior that occurred in early stimulation of chronic unpredictable mild stress.