Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, P. R. China.
Ups J Med Sci. 2013 Mar;118(1):3-8. doi: 10.3109/03009734.2012.724118. Epub 2012 Sep 13.
Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR).
Forty male Wistar rats weighing 180-220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels.
Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses)
The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats.
先前的研究表明，单次亚麻醉剂量的氯胺酮可在患者和抑郁动物模型中发挥快速抗抑郁作用。然而，其潜在机制尚不完全清楚。本研究旨在探讨不同剂量氯胺酮急性给药对强迫游泳试验中大鼠不动时间的影响，并确定海马脑源性神经营养因子（BDNF）和哺乳动物雷帕霉素靶蛋白（mTOR）的水平。
40 只雄性 Wistar 大鼠，体重 180-220 g，随机分为 4 组（每组 10 只）：盐水组和氯胺酮 5、10 和 15 mg/kg 组。第一天，所有动物均强迫游泳 15 分钟。第二天，分别给予氯胺酮（5、10 和 15 mg/kg），在第二次强迫游泳试验前 30 分钟腹膜内给药。记录大鼠在强迫游泳试验中的不动时间。然后处死动物。采集海马组织，用于测定 BDNF 和 mTOR 水平。
与盐水组相比，氯胺酮 5、10 和 15 mg/kg 剂量给药均可降低不动时间（所有剂量 P < 0.05）。氯胺酮 10 和 15 mg/kg 剂量均可显著增加海马 BDNF 的表达（两个剂量均 P < 0.05）。氯胺酮 5、10 和 15 mg/kg 剂量给药均可显著增加海马 p-mTOR 的相对水平（所有剂量均 P < 0.05）。
氯胺酮的抗抑郁作用可能与大鼠海马 BDNF 和 mTOR 表达增加有关。
