Background: Depression affects various brain functions. According to previous studies, escitalopram influences brain functions in depression and crocin reduces memory impairments. Therefore, this study aimed to compare the therapeutic effects of using crocin and escitalopram (separately and in combination) on learning and memory in rats with stress-induced depression. Methods: Fifty-six rats were allocated into seven groups of control, sham, continuous depression, recovery period, daily injections of escitalopram, crocin and escitalopram-crocin during 14 days after inducing depression by stress. Passive avoidance (PA) test was used to assess brain functions. Results: Latency has significant differences in depression group. Also, it significantly increased in depression-crocin, depression-escitalopram and depression-escitalopram-crocin groups compared to the depression group. The dark stay (DS) time was significantly higher in the depression and depression-recovery groups. However, the DS time significantly decreased in the depression-crocin, depression-escitalopram and depression-escitalopram-crocin groups. Furthermore, the number of entrances to the dark room was significantly lower in depression-crocin and depression-escitalopram-crocin groups compared to the depression one. Conclusion: Different depression treatments (i.e. crocin, escitalopram and crocin- escitalopram) reduced depression-induced memory deficits. Crocin and escitalopram-crocin, respectively, improved brain functions and locomotor activity more than escitalopram. Comparatively, in subjects with depression, crocin, which is an effective saffron constituent, partially affected the memory deficits better than escitalopram (as a chemical component).
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