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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Objectives:</i></b> To analyze the process of working memory and cognitive flexibility impairments in a rat model of depression. <b><i>Methods:</i></b> In this experimental study, chronic unpredictable mild stress (CUMS) was used as a model of depression in 30 rats (<i>Rattus novergicus</i>). Cognitive function was assessed with the <i>Morris water maze</i> and <i>attentional set shifting test</i>. <b><i>Results:</i></b> This study found a significant difference on day 21 in working memory (<i>p</i> = 0.002) and cognitive flexibility (<i>p</i> = 0.036), which continued to day 41 in working memory (<i>p</i> = 0.001) and cognitive flexibility (<i>p</i> = 0.020). In the CUMS model of depression, parameters peak on day 41 and reveal parameter changes in weight gain (<i>p</i> = 0.018), food intake (<i>p</i> &#x3c; 0.001), changes in food intake (<i>p</i> = 0.001), and the sucrose preference (<i>p</i> = 0.005), elevated plus maze (<i>p</i> = 0.001), and light dark box tests (<i>p</i> = 0.020). <b><i>Conclusion:</i></b> 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.