氯胺酮对强迫游泳大鼠海马谷氨酸、NR2A及NR2B的影响

Effects of ketamine on glutamate, NR2A, and NR2B in the hippocampus of rats subjected to forced swimming tests

目的观察氯胺酮对强迫游泳大鼠海马组织中谷氨酸及N-甲基-D-天冬氨酸(NMDA)受体亚型NR2A、NR2B水平的影响。方法雄性Wistar大鼠50只,随机均分为5组(n=10):对照组(C组)和不同剂量氯胺酮组(K1-K4组)。强迫游泳15min建立大鼠抑郁模型,次日分别经腹腔注射氯胺酮2.5mg/kg(K1组)、5.0mg/kg(K2组)、10.0mg/kg(K3组)、20.0mg/kg(K4组)或生理盐水1.0ml(C组),给药后30min再次强迫游泳5min,观察并记录不动时间。行为学测试后,取各组大鼠海马组织,采用ELISA法测定谷氨酸、NR2A及NR2B的含量。结果与C组比较,K1-K4组强迫游泳不动时间减少,且与氯胺酮用量呈明显负相关(r=-0.913,P<0.001);K1-K4组海马谷氨酸含量明显增高,NR2B含量明显减少(P<0.01),而NR2A含量与C组比较无明显差异(P>0.05)。结论氯胺酮具有显著的抗抑郁作用,可能与海马谷氨酸及NR2B的含量变化有关。

Objective To observe the effects of ketamine on glutamate, N-methyl-D-aspartic acid receptor （NMDA） subunits NR2A,and NR2B in the hippocampus of rats subjected to a forced swimming test（FST）.Methods A total of 50 male Wistar rats were equally randomized into（n=10 each） the control（C） group and the ketamine1 to ketamine 4（K1 to K4） groups （different ketamine dosage）.An FST of 15 min was used to reproduce a rat depression model.On the next day,1.0ml of saline 1.0 （group C） and 2.5（Group K1）,5.0（Group K2）,10.0（Group K3）,and 20.0mg/kg of ketamine（Group K4） were intraperitoneally injected.After 30min,a 5min FST was carried out.The immobility time of the rats during the FST was recorded.The animals were then decapitated and their hippocampi were harvested to determine the concentrations of glutamate,NR2A,and NR2B using an enzyme-linked immunosorbent assay.Results Compared with group C,groups K1–K4 had lower immobility times during FST,and it was inversely related to the ketamine dosage（r=-0.913,P0.001）.Groups K1–K4 also had increased glutamate concentrations and decreased NR2B concentrations （P0.01） in hippocampus. The NR2A concentrations were not statistically significantly different among the groups（P0.05）.Conclusion Ketamine possesses significant antidepressant effects,which may be potentially attributed to the changes in the glutamate and NR2B concentrations in the hippocampus.