Antidepressant-Like Effect of Lipid Extract of Channa striatus in Chronic Unpredictable Mild Stress Model of Depression in Rats

Abstract

This study evaluated the antidepressant-like effect of lipid extract of C. striatus in chronic unpredictable mild stress (CUMS) model of depression in male rats and its mechanism of action. The animals were subjected to CUMS for six weeks by using variety of stressors. At the end of CUMS protocol, animals were subjected to forced swimming test (FST) and open field test followed by biochemical assay. The CUMS protocol produced depressive-like behavior in rats by decreasing the body weight, decreasing the sucrose preference, and increasing the duration of immobility in FST. The CUMS protocol increased plasma corticosterone and decreased hippocampal and prefrontal cortex levels of monoamines (serotonin, noradrenaline, and dopamine) and brain-derived neurotrophic factor. Further, the CUMS protocol increased interleukin-6 (in hippocampus and prefrontal cortex) and nuclear factor-kappa B (in prefrontal cortex but not in hippocampus). The lipid extract of C. striatus (125, 250, and 500 mg/kg) significantly (p < 0.05) reversed all the above parameters in rats subjected to CUMS, thus exhibiting antidepressant-like effect. The mechanism was found to be mediated through decrease in plasma corticosterone, increase in serotonin levels in prefrontal cortex, increase in dopamine and noradrenaline levels in hippocampus and prefrontal cortex, increase in BDNF in hippocampus and prefrontal cortex, and decrease in IL-6 and NF-κB in prefrontal cortex.

Figure 1

CUMS study scheme and timeline.

Figure 2

Body weight of rats subjected to chronic unpredictable mild stress. Data represent mean (g) ± SEM (n = 6–8); ^### p < 0.001 when compared to no stress group; ^∗ p < 0.05, ^∗∗ p < 0.01, and ^∗∗∗ p < 0.001 when compared to CUMS control group; one-way ANOVA followed by Tukey's multiple comparison test.

Figure 3

Sucrose preference of rats subjected to chronic unpredictable mild stress. Data represent mean (%) ± SEM (n = 6–8); ^# p < 0.05, ^## p < 0.01, and ^### p < 0.001 when compared to no stress group; ^∗ p < 0.05, ^∗∗ p < 0.01, and ^∗∗∗ p < 0.001 when compared to CUMS control group; one-way ANOVA followed by Tukey's multiple comparison test.

Figure 4

(a) Effect of lipid extract of C. striatus fillets and fluoxetine in rats subjected to chronic unpredictable mild stress model of depression in forced swimming test. (b) and (c) Effect of lipid extract of C. striatus fillets and fluoxetine in rats subjected to chronic unpredictable mild stress model of depression in open field test. Data represent mean ± SEM (n = 6–8). ^# p < 0.05 when compared with no stress group; ^∗ p < 0.05, ^∗∗ p < 0.01, and ^∗∗∗ p < 0.001 when compared with CUMS control group; one-way ANOVA followed by Tukey's multiple comparison test.

Figure 5

(a) Effect of lipid extract of C. striatus fillets and fluoxetine in rats subjected to chronic unpredictable mild stress model of depression on plasma corticosterone level. (b) Effect of lipid extract of C. striatus fillets and fluoxetine in rats subjected to chronic unpredictable mild stress model of depression on plasma oxytocin level. Data represent mean ± SEM (n = 6–8). ^## p < 0.05 when compared with no stress group; ^∗ p < 0.05 and ^∗∗ p < 0.01 when compared with CUMS control group. One-way ANOVA followed by Tukey's multiple comparison test.

Figure 6

Effect of lipid extract of C. striatus fillets and fluoxetine on serotonin level in hippocampus (a), serotonin level in prefrontal cortex (b), noradrenaline level in hippocampus (c), noradrenaline level in prefrontal cortex (d), dopamine level in hippocampus (e), and dopamine level in prefrontal cortex (f) in rats subjected to chronic unpredictable mild stress model of depression. Data represent mean ± SEM (n = 6–8). ^# p < 0.05, ^## p < 0.01, and ^### p < 0.001 when compared with no stress group; ^∗ p < 0.05, ^∗∗ p < 0.01, and ^∗∗∗ p < 0.001 when compared with CUMS control group. One-way ANOVA followed by Tukey's multiple comparison test.

Figure 7

Effect of lipid extract of C. striatus fillets and fluoxetine on BDNF level in hippocampus (a) and BDNF level in prefrontal cortex (b), IL-6 level in hippocampus (c), IL-6 level in prefrontal cortex (d), NF-κB level in hippocampus (e), and NF-κB level in prefrontal cortex (f) in rats subjected to chronic unpredictable mild stress model of depression. Data represent mean ± SEM (n = 6–8). ^# p < 0.05, ^## p < 0.01, and ^### p < 0.001 when compared with no stress group; ^∗ p < 0.05, ^∗∗ p < 0.01, and ^∗∗∗ p < 0.001 when compared with CUMS control group. One-way ANOVA followed by Tukey's multiple comparison test.