γ-氨基丁酸在氯胺酮抗抑郁中的作用  

Role of gamma-aminobutyric acid in the antidepressant effects of ketamine

作　　者：刘向六[1] 刘文学[1] 邱丽丽[1] 张广芬[1] 周志强[1] 

机构地区：[1]南京大学医学院附属金陵医院(南京军区南京总医院)麻醉科,南京210002

出　　处：《医学研究生学报》2015年第1期4-6,共3页Journal of Medical Postgraduates

基　　金：国家自然科学基金(30872424);全军医学科学技术研究"十二五"发展计划课题(CWS11J017)

摘　　要：目的近年来研究发现亚麻醉剂量氯胺酮具有快速有效的抗抑郁作用,但具体机制不清楚。观察γ-氨基丁酸(gamma-aminobutyric acid,GABA)在氯胺酮抗抑郁中的作用。方法 32只Wistar雄性大鼠随机均分为4组(n=8):等渗盐水组、氯胺酮组、GABA组、GABA+氯胺酮组。所有大鼠均行侧脑室置管,术后第8天行强迫游泳15 min制备急性应激抑郁模型。造模后24 h,等渗盐水组及氯胺酮组侧脑室给予等渗盐水2μL,GABA组及GABA+氯胺酮组侧脑室给予GABA 50μg(2μL),10 min后等渗盐水组及GABA组腹腔注射等渗盐水1 m L,氯胺酮组及GABA+氯胺酮组腹腔注射氯胺酮10 mg/kg(1 m L)。30 min后行敞箱实验记录大鼠水平运动及垂直运动得分,行强迫游泳实验6 min记录后5 min内不动时间。行为学测试结束后,取大鼠前额皮层,检测GABA的含量。结果等渗盐水组、GABA组、GABA组+氯胺酮组大鼠不动时间[(167.2±22.1)、(159.8±17.5)、(143.8±22.1)s]均较氯胺酮组[(107.5±21.2)s]长(P<0.05);与GABA组比较,GABA+氯胺酮组大鼠不动时间差异无统计学意义(P>0.05)。等渗盐水组、GABA组、GABA+氯胺酮组大鼠前额皮层GABA含量[(23.3±6.3)、(27.3±5.7)、(18.0±5.4)ng/mg·prot]均较氯胺酮组[(12.4±3.4)ng/mg·prot]升高(P<0.05);与GABA组比较,GABA+氯胺酮组大鼠前额皮层GABA含量减少[(27.3±5.7)ng/mg·prot vs(18.0±5.4)ng/mg·prot,P<0.05]。4组大鼠水平运动及垂直运动OFT得分差异均无统计学意义(P>0.05)。结论在大鼠强迫游泳模型中,氯胺酮的抗抑郁作用与前额皮层GABA下调有关。Objective Accumulating evidence has demonstrated that the sub-anesthetic dose of ketamine exerts rapid and ro-bust antidepressant-like effects though its action mechanisms are not yet fully understood .The aim of this study was to investigate the role of gamma-aminobutyric acid （ GABA） in the antidepressant effects of ketamine . Methods Thirty-two male Wistar rats were e-qually randomized into four groups： saline, ketamine, GABA, and GABA＋ketamine.All the animals were implanted with a guide cannula into the lateral ventricle and on the eighth day after operation subjected to a 15 min forced swimming test （FST） for the estab-lishment of a depression model .At 24 h after modeling , the rats of the saline and ketamine groups were treated intracerebroventricularly with 2μL isotonic saline solution, and those of the GABA and GABA ＋ketamine groups with 50μg （2μL） GABA, followed by intrap-eritoneal administration of 1 mL saline in the former two groups and 10 mg/kg （1 mL） ketamine in the latter two groups 10 min later.At 30 min after treatment , the open field test （ OFT） was carried out for crossing and rearing scores and a 6-min FST was performed to re-cord the immobility time in the last 5 minutes.The content of GABA in the prefrontal cortex of the rats was measured following behav -ioral tests. Results The immobility time was significantly decreased in the ketamine group （[107.5 ±21.2]sec） as compared with the saline, GABA, and GABA＋ketamine groups （[167.2 ±22.1], [159.8 ±17.5], and [143.8 ±22.1]sec） （P0.05）.The level of GABA in the prefrontal cortex was remarkably lower in the ketamine group （[12.4 ±3.4]ng/mg prot） than in the saline, GABA, and GABA＋ketamine groups （[23.3 ± 6.3], [27.3 ±5.7], and [18.0 ±5.4]ng/mg prot） （P0.05 ）. Conclusion The antidepressant effects of ketamine are related to the decreased GABA level in the prefrontal cortex in rats receiving FST .

关 键 词：氯胺酮 抑郁 前额皮层 Γ-氨基丁酸 

分 类 号：R965[医药卫生—药理学]