重复经颅磁刺激联合舍曲林对CUS大鼠抑郁样行为和大脑皮层5-HIAA与5-HT水平的影响

Influence of repetitive transcranial magnetic stimulation combined with sertraline on depressive-like behavior and levels of 5-HT and 5-HIAA in cortex of CUS rats

目的探讨重复性经颅磁刺激（rTMS）联合舍曲林对慢性不可预见应激（CUS）大鼠抑郁样行为的改善作用及对其大脑皮层5-羟吲哚乙酸（5-HIAA）和5-羟色胺（5-HT）表达的影响。方法采用随机数字表法将40只雄性SD大鼠分为5组：Sham组、CUS组、CUS＋rTMS组、CUS＋Ser组以及CUS＋rTMS＋Ser组，每组8只。Sham组正常饲养28d后，给予连续7d的rTMS假刺激；其余4组建立CUS大鼠模型，CUS组和CUS＋Ser组连续7d给予rTMS假刺激，CUS＋rTMS组和CUS＋rTMS＋Ser组连续7d给予相同频率和强度的rTMS刺激。此外，CUS＋Ser组和CUS＋rTMS＋Ser组连续7d腹腔注射舍曲林[10mg／（kg·d）]，其余组连续7d腹腔注射相同剂量的生理盐水。随后进行糖水偏好实验和旷场实验，评估大鼠的抑郁样行为。在行为学检测结束后，处死大鼠，采用酶联免疫吸附法（EUSA）测定各组大鼠皮层5-HIAA和5-HT的水平。结果（1）CUS组糖水偏好值低于其他处理组（P〈0．05）；但CUS＋rTMS组、CUS＋Ser组与CUS＋rTMS＋Ser组两两比较差异均无统计学意义（尸〉0．05）。（2）cus组中央区运动距离百分比和中央区探索时间均低于其他处理组（P〈0．05），且CUS＋rTMS组和CUS＋Ser组之间差异无统计学意义（P〉0．05）。（3）与CUS组相比，Sham组、CUS＋rTMS组和CUS＋rTMS＋Ser组大鼠皮层中5-HIAA的含量降低（P〈0．01）；且CUS＋Ser组与CUS＋rTMS＋Ser组之间的差异有统计学意义（P〈0．05）；CUS组5-HT水平低于其他组（P〈0．05）。结论rTMS联合舍曲林能改善CUS动物的抑郁样行为，其作用可能是通过下调CUS模型大鼠5-HIAA，上调5-HT水平实现的。

Objective To investigate the antidepressive effects of repetitive Transcranial Magnetic Stimulation （rTMS） combined with Sertraline （Ser） in rat model of Chronic Unpredictable Stress （CUS） rats as well as the influence on levels of 5-HIAA and 5-HT in cortex. Methods Totals of 40 adult male Sprague Dawley rats were randomly divided into five groups： Sham group, CUS group, CUS＋rTMS group, CUS＋S- er group and CUS＋rTMS＋Ser group. Rats in Sham group were treated with fake rTMS for consecutive 7 d after 28 d normal breeding. Rats in CUS group and CUS＋Ser group were treated with fake rTMS for consecutive 7 d after successful modeling. And rats in CUS＋rTMS group and CUS＋rTMS＋Ser group were treated with rTMS with the same frequency and intensity of rTMS stimulation for consecutive 7 d after successful modeling. In addition, rats in CUS＋Ser group and CUS＋rTMS＋Ser group received Ser [ 10 mg/（kg·d）] intraperitoneally injection for 7 d and other groups were injected intraperitoneally with the same dose of saline. Then the sugar preference test and open field test were performed to examine the behaviors. Meanwhile, at the end of the behavioral test, rats were sacrificed and the levels of 5-HIAA and 5-HT in cortex were measured by Enzyme Linked Immunosorbent Assay （ELISA）. Results （1） The sucrose preference percentage of the CUS group was significantly less than that of other groups （P 〈 0.05）. But there were no significant differences between CUS＋rTMS group, CUS＋Ser group and CUS＋rTMS＋Ser group （P 〉 0.05）. （2） The fraction of central distance and the time exploring in center of the CUS group was significantly reduced than that of other groups （P 〈 0.05）. And there was no significant difference between CUS＋rTMS group and CUS＋Ser group （P 〉 0.05）. （3） Compared with CUS group, the cortical levels of 5-HIAA in CUS＋rTMS and CUS＋rTMS＋Ser group were significantly reduced （P 〈 0.01）. And there was signif- icant difference between CUS＋Ser group and CUS＋rTMS＋Ser group （P 〈 0.05）. Meanwhile, the levels of 5-HT in CUS group was significantly reduced than that of other groups （P 〈 0.05）. Conclusions rTMS combined with Sertraline could ameliorate the depression-like behavior of CUS rats and this effect may be related with the up-regulation of 5-HT and down-regulating of 5-HIAA in cortex.