CAJ | 학술논문

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），10min 后等渗盐水组及GABA组腹腔注射等渗盐水1 mL，氯胺酮组及GABA＋氯胺酮组腹腔注射氯胺酮10 mg／kg （1 mL）。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。
목적：근년래연구발현아마취제량록알동구유쾌속유효적항억욱작용，단구체궤제불청초。관찰γ-안기정산（gamma-aminobutyric acid， GABA）재록알동항억욱중적작용。방법32지Wistar웅성대서수궤균분위4조（n＝8）：등삼염수조、록알동조、GABA조、 GABA ＋록알동조。소유대서균행측뇌실치관，술후제8천행강박유영15 min제비급성응격억욱모형。조모후24 h，등삼염수조급록알동조측뇌실급여등삼염수2μL ，GABA조급GABA＋록알동조측뇌실급여 GABA 50μg （2μL），10min 후등삼염수조급GABA조복강주사등삼염수1 mL，록알동조급GABA＋록알동조복강주사록알동10 mg／kg （1 mL）。30 min후행창상실험기록대서수평운동급수직운동득분，행강박유영실험6 min기록후5 min내불동시간。행위학측시결속후，취대서전액피층，검측GABA적함량。결과등삼염수조、GABA조、GABA조＋록알동조대서불동시간[（167．2±22．1）、（159．8±17．5）、（143．8±22．1）s]균교록알동조[（107．5±21．2）s]장（P＜0．05）；여GABA조비교，GABA＋록알동조대서불동시간차이무통계학의의（ P＞0．05）。등삼염수조、GABA조、GABA＋록알동조대서전액피층GABA함량[（23．3±6．3）、（27．3±5．7）、（18．0±5．4）ng／mg·prot ]균교록알동조[（12．4±3．4）ng／mg·prot ]승고（P＜0．05）；여GABA조비교， GABA＋록알동조대서전액피층GABA함량감소[（27．3±5．7）ng／mg· prot vs （18．0±5．4）ng／mg· prot， P＜0．05]。4조대서수평운동급수직운동OFT득분차이균무통계학의의（P＞0．05）。결론재대서강박유영모형중，록알동적항억욱작용여전액피층GABA하조유관。
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) (P<0.05), with no significant difference between the GABA and GABA +ketamine groups (P>0.05).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) (P<0.05), but markedly higher in the GABA than in the GABA +ketamine group (P<0.05).OFT scores exhibited no significant difference in the lo-comotor activity among the four groups of rats ( P >0.05 ). Conclusion The antidepressant effects of ketamine are related to the decreased GABA level in the prefrontal cortex in rats receiving FST .