Comparative Evaluation of Antidepressant and Anxiolytic Effects of Escitalopram, Crocin, and their Combination in Rats

Abstract

Background: Chronic stress can lead to anxiety and depression. Escitalopram is a selective serotonin reuptake inhibitor (SSRI), and crocin is a natural compound derived from saffron. Both of them are used to treat these disorders in clinical and traditional medicine, respectively. This study compared the antidepressant and anxiolytic effects of escitalopram, crocin, and their combination in rats.

Materials and methods: Rats were divided into nine groups: control, sham, rest-depression, depression-rest, depression-crocin, depression-escitalopram10, depression-escitalopram20, depression-escitalopram10-crocin, and depression-escitalopram20-crocin. Forced swimming and open field tests (FST and OFT, respectively) were used to evaluate depression, anxiety, and locomotor activity.

Results: In the FST, the immobility time on day 28 significantly decreased in all depressed groups that received escitalopram, crocin, and their combination compared to the rest-depression group. Whereas, conversely, the time spent at the center in the OFT was significantly higher in similar comparisons. The total distance traveled by the OFT was significantly lower in all depressed groups, except for the depression-escitalopram10 and depression-escitalopram20 groups. The total distance traveled was significantly higher in the depression-escitalopram20 compared to the rest-depression group.

Conclusion: Crocin, both doses of escitalopram and their combination, reduced depression. A high dose of escitalopram, with and without crocin, was partially more effective than a low dose of escitalopram in reversing depression. There was anxiety-like behavior observed after inducing depression with and without a recovery period. Whereas, crocin alone and both doses of escitalopram, with and without crocin, decreased anxiety-like behaviors in subjects with depression. This effect may be attributed to a modulation of brain neurotransmitter ratios.

Keywords: Crocin; depression; escitalopram; immobilization; stress.

Figure 1

Schematic diagram of the experimental protocol designs. There were two types of behavioral tests, including the forced swimming test (FST) and the open field test (OFT)

Figure 2

The immobility times of the forced swim test (FST) on days (a) 14 and (b) 28 were measured in all experimental groups (n = 8). Results are expressed as means ± SEM (one-way ANOVA followed by Tukey's post-hoc test). ***P < 0.001 compared to the Con group; ^###P < 0.001 compared to the Sh group; ^ϴP < 0.05, ^ϴϴP < 0.01 and ^ϴϴϴP < 0.001 compared to the Rest-Dep group; ^ℓP < 0.05 compared to the Dep-Rest group

Figure 3

The immobility time on the 14^th and 28^th day of the forced swim test or FST (within-group) was measured in each group (n = 8). Results are expressed as mean ± SEM (paired sample t-test). ⁺⁺P < 0.01 and ⁺⁺⁺P < 0.001 the immobility time of day 14 relative to the immobility time of day 28

Figure 4

The center time(s) of the open field test (OFT) was measured in all experimental groups. Results are expressed as means ± SEM (one-way ANOVA followed by Tukey's post-hoc test). *P < 0.05 and **P < 0.01 compared to the Con group; ^#P < 0.05 and ^##P < 0.01 compared to the Sh group; ^ϴP < 0.05, ^ϴϴP < 0.01 and ^ϴϴϴP < 0.001 compared to the Rest-Dep group; and ^ℓP < 0.05 and ^ℓℓℓP < 0.001 compared to the Dep-Rest group

Figure 5

The total distance traveled (in cm) in the open field test (OFT) was measured for all experimental groups (n = 8). Results are expressed as means ± SEM (one-way ANOVA followed by Tukey's post-hoc test). *P < 0.05, **P < 0.01, and ***P < 0.001 compared to the Con group; ^#P < 0.05, ^##P < 0.01, and ^###P < 0.001 compared to the Sh group; ^ϴϴϴP < 0.001 compared to the Rest-Dep group; and ^ℓP < 0.05 compared to Dep-Rest group; ^£P < 0.05 compared to Dep-Cr group