Chen Jing, Peng Li-Hua, Luo Jie, Liu Li, Lv Feng, Li Ping, Ao Li, Hao Xue-Chao, Min Su
From the Department of Anesthesia and Pain Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
J ECT. 2015 Mar;31(1):50-6. doi: 10.1097/YCT.0000000000000148.
To investigate the effects of low-dose ketamine combined with propofol on the antidepressant efficacy in stressed rats undergoing electroconvulsive shock (ECS) and its impact on phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor subunit glutamate receptor 1 (GluR1) and γ-aminobutyric acid receptor subunit A (GABAAR).
Sprague-Dawley rats were stressed by chronic unpredictable mild stress. Fifty stressed rats were randomly divided into 5 groups (n = 10 per group): depression group (with no application, group D), ECS group (applied with ECS after intraperitoneal injection of isotonic sodium chloride solution, 8 mL/kg, group E), ketamine + ECS group (applied with ECS after intraperitoneal injection of ketamine, 10 mg/kg, group KE), propofol + ECS group (applied with ECS after intraperitoneal injection of propofol, 80 mg/kg, group PE), and ketamine + propofol + ECS group (applied with ECS after intraperitoneal injection of ketamine, 10 mg/kg, and propofol, 80 mg/kg, group KPE). All groups except group D underwent ECS once a day for 7 consecutive days. Sucrose preference test, open-field test, and Morris water maze were performed to assess the depressive behavior. Phosphorylation of GluR1 and GABAAR were evaluated by Western blot.
Compared with group D, sucrose preference percentage and open-field scores were increased after ECS application in the 4 other groups; rats in group E reported prolonged escape latency and shortened space exploration time, whereas the escape latency were decreased and space exploration time were prolonged in group KPE; the ratio of p-GluR1/p-GABAAR in hippocampus were increased in the 4 other groups. When using group E as control, rats in group KPE exhibited higher sucrose preference percentage and open-field scores; the escape latency was shortened and space exploration time was prolonged in groups KE, PE, and KPE; the ratio of p-GluR1/p-GABAAR in the hippocampus was up-regulated in groups KE and KPE. When compared with groups KE and PE, the rats in group KPE exhibited higher sucrose preference percentage and open-field scores, the escape latency of group KPE was shortened and space exploration time was prolonged, the ratio of p-GluR1/p-GABAAR in the hippocampus of group KEP is between those of groups KE and PE.
Low-dose ketamine combined with propofol may play a role in enhancing the antidepressant efficacy of ECS in stressed rats, ameliorating the cognitive impairment associated with ECS by balancing the expression of p-GluR1 and p-GABAAR in the hippocampus of stressed rats.
探讨小剂量氯胺酮联合丙泊酚对接受电休克（ECS）应激大鼠抗抑郁疗效的影响及其对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基谷氨酸受体1（GluR1）和γ-氨基丁酸受体亚基A（GABAAR）磷酸化的影响。
采用慢性不可预测温和应激法对Sprague-Dawley大鼠进行应激。将50只应激大鼠随机分为5组（每组n = 10）：抑郁组（未处理，D组）、ECS组（腹腔注射等渗氯化钠溶液8 mL/kg后给予ECS，E组）、氯胺酮+ECS组（腹腔注射氯胺酮10 mg/kg后给予ECS，KE组）、丙泊酚+ECS组（腹腔注射丙泊酚80 mg/kg后给予ECS，PE组）、氯胺酮+丙泊酚+ECS组（腹腔注射氯胺酮10 mg/kg和丙泊酚80 mg/kg后给予ECS，KPE组）。除D组外，所有组连续7天每天接受1次ECS。进行蔗糖偏好试验、旷场试验和Morris水迷宫试验以评估抑郁行为。通过蛋白质免疫印迹法评估GluR1和GABAAR的磷酸化情况。
与D组相比，其他4组在给予ECS后蔗糖偏好百分比和旷场得分增加；E组大鼠逃避潜伏期延长，空间探索时间缩短，而KPE组逃避潜伏期缩短，空间探索时间延长；其他4组海马中p-GluR1/p-GABAAR的比值增加。以E组为对照，KPE组大鼠蔗糖偏好百分比和旷场得分更高；KE组、PE组和KPE组逃避潜伏期缩短，空间探索时间延长；KE组和KPE组海马中p-GluR1/p-GABAAR的比值上调。与KE组和PE组相比，KPE组大鼠蔗糖偏好百分比和旷场得分更高，KPE组逃避潜伏期缩短，空间探索时间延长，KEP组海马中p-GluR1/p-GABAAR的比值介于KE组和PE组之间。
小剂量氯胺酮联合丙泊酚可能通过平衡应激大鼠海马中p-GluR1和p-GABAAR的表达，增强ECS对应激大鼠的抗抑郁疗效，改善与ECS相关的认知障碍。
