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| Study on the antidepressant effects of tubacin for the model rats with chronic unpredictable mild stress and its mechanism |
| SUN Guoping1 LI Kun2 LU Haozhong1 XUE Xiaobin1 |
1.Qingdao Mental Health Center, Shandong Province, Qingdao 266034, China;
2.Pharmacy Intravenous Admixture Services, Qilu Hospital of Shandong University (Qingdao), Shandong Province, Qingdao 265000, China |
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Abstract Objective To investigate the antidepressant effects of histone deacetylase 6 (HDAC6) selective inhibitor tubacin for the model rats with chronic unpredictable mild stress (CUMS) and its mechanism. Methods Fifty male adult rats were randomly divided into 5 groups (n = 10): control group (group A), CUMS model group (group B), Fluoxetine treatment group (group C), tubacin treatment group (group D) and combination of Fluoxetine and tubacin treatment group (group E). The spatial learning and memory abilities of rats were tested by orientation navigation experiment and spatial probe trial of Morris water maze. Meanwhile, the levels of serum reduced glutathione (GSH) in all groups were measured by GSH kits. Results The orientation navigation experiment of Morris water maze showed that compared with group A, the mean escape latency of rats in group B was significantly lengthened (P ＜ 0.05 or P ＜ 0.01), compared with group B, the mean escape latency of rats in group C, D, E was significantly shortened (P ＜ 0.05 or P ＜ 0.01), and the mean escape latency of rats in group E was significantly shorter than those of group C, D (P ＜ 0.05 or P ＜ 0.01). In the spatial probe trial, the length of stay in the third quadrant of group C, D, E was significantly longer than those of the left three quadrants (P ＜ 0.05 or P ＜ 0.01), the length of stay in the third quadrant of group E was significantly longer than those of group C, D (P ＜ 0.01, P ＜ 0.05). The level of serum GSH in group B was significantly lower than that of group A (P ＜ 0.05), while the level of serum GSH in group C was significantly higher than that of group B (P ＜ 0.05), the level of serum GSH in group E was significantly higher than that of group C (P ＜ 0.05), there was no statistically significant difference between group E and group A (P ＞ 0.05). Correlation analysis showed that the spatial learning and memory abilities of rats were significantly correlated with the level of GSH (P ＜ 0.05). Conclusion HDAC6 selective inhibitor tubacin can improve the spatial learning and memory abilities of rats by regulating the levels of GSH, so as to play antidepressant effects.
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