目的 探讨不同剂量氯胺酮对强迫游泳大鼠抗抑郁效应的影响及其潜在机制.方法 40只2月龄雄性Wistar大鼠随机均分为4组(n=10),行强迫游泳实验(forced swimming test,FST)15 min以建立大鼠抑郁模型.次日,分别腹腔注射生理盐水、氯胺酮5 mg/kg、氯胺酮10 mg/kg、氯胺酮20 mg/kg.30 min后,行FST5 min并记录其不动时间.行为学测试后,取海马组织测定雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)及谷氨酸受体1(glumate receptor 1,GluR1)的含量.结果 氯胺酮5 mg/kg组、10 mg/kg组和20 mg/kg组大鼠强迫游泳不动时间分别为136±13 s、119±12 s和95 ±20 s,与对照组的169±12 s相比,各组氯胺酮大鼠强迫游泳不动时间明显减少且呈剂量依赖性,P<0.05;各组氯胺酮大鼠海马组织mTOR含量分别为1.52±0.19、2.36±0.13和2.95±0.22.较对照组的0.87±0.11显著增高,P<0.05;各组氯胺酮大鼠海马组织GluR1含量分别为1.23 ±0.11、1.45 ±0.06和1.60±0.13,亦较对照组的0.91±0.07显著增高,P<0.05.结论 氯胺酮具有确切的抗抑郁作用,其机理可能与海马组织mTOR及GluR1的上调有关.%Objective To investigate the antidepressant effects of different doses of ketamine of rats undergoing the forced swimming test and to elucidate its potential underlying mechanisms. Methods Forty male Wistar rats weighing 180 ~ 220 g were equally randomized into 4 groups (n = 10 each). The forced swimming test (FST) for 15 min was used to establish a rat depression model. On the 2rd day, animals received intraperitoneal injection of saline, ketamine 5 mg/kg, 10 mg/kg, or 15 mg/kg, respectively. Thirty minutes later, the rat immobility time was recorded during additional 5min FST. The hippocampus was harvested for determination of mammalian target of rapa-mycin (mTOR) and glu-tamate receptor 1 (GluRl) levels. Results Compared with saline group (169 ± 12 s), rats receiving ketamine (136 ± 13 s, 119 ± 12 s, or 95 ± 20 s) showed significant decrease in immobility during FST in a dose-dependent manner (P < 0.05). Rats receiving ketamine showed significant increase in the expression of mTOR (group saline; 0.87 ± 0.11; group ketamine: 1.52 ± 0.19, 2.36 ± 0.13, 2.95 ± 0.22) and GluRl (group saline; 0.91 ± 0.07; group ketamine: 1.23 ± 0.11, 1.45 ± 0.06, 1.60 ± 0.13)in the hippocampus as compared with group C (P < 0.05). Conclusion Ketamine exerts antidepressant effects probably through upregulation of mTOR and GluRl in the rat hippocampus.
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