多次氯胺酮麻醉对发育早期大鼠空间辨别学习记忆与海马CA1区突触长时程增强的影响

Effect of repeated ketamine administration on long-term potentiation (LTP) in area CA1 of hippocampal slices of early developing rats

目的观察分别单次或多次给予发育早期大鼠腹腔注射氯胺酮70mg·kg-1对大鼠学习记忆的影响。方法发育早期大鼠70只,随机分为5组。Con1组大鼠单次腹腔注射生理盐水2ml。Con2组大鼠每3天腹腔注射生理盐水2ml1次,共5次。Ket1组大鼠单次腹腔注射氯胺酮70mg·kg-1。Ket3组大鼠每3天腹腔注射氯胺酮70mg·kg-11次,共3次。Ket5组大鼠每3天腹腔注射氯胺酮70mg·kg-11次,共5次。末次给药7天后,分别运用水迷宫实验(n=8)及电生理海马脑片细胞外记录技术记录海马CA1区突触长时程增强(long-termpotentiation,LTP)(n=6),观测发育早期大鼠每3天分别腹腔注射氯胺酮70mg·kg-1(1、3、5次)7天后对大鼠学习记忆的影响。结果发育早期大鼠单次或多次氯胺酮70mg·kg-1腹腔注射7天后,与生理盐水组相比,单次应用氯胺酮后大鼠海马脑片CA1区强直刺激后群峰电位振幅(PSA)与LTP诱发率无显著性差异(P>0.05),但多次用药后强直刺激后PSA与LTP诱发率均明显降低(P<0.01)。而水迷宫实验大鼠达标所需训练次数、逃避潜伏期、进入盲端次数组间无显著性差异(P>0.05)。结论多次氯胺酮腹腔注射可能引起7天后大鼠学习记忆功能损害,但此学习记忆的损害并不表现为大鼠空间辨别学习记忆功能的损害。

Objective To investigate the effect of repeated ketamine administration on learning and memory in early developing rats.?Methods Early developing rats were randomly divided into 5 groups. The rats were administered normal saline 2 ml ip once in group Con1 and 2 ml ip q3d for 5 times in group Con2, while the others were given ketamine 70 mg·kg^-1 ip once, and q3d for 3 times and 5 times in groups Ket1,Ket3 and Ket5 respectively. Seven days after the last drug injection, behavior and electrical physiological techniques were employed to define the impact of repeated use of ketamine on learning and memory in early developing rats.?Results Electrophysiology of the hippocampal slice showed repeated ketamine administration in group Ket5 decreased the population spike amplitude (PSA) and the induction rate of LTP (P<0.01).However,repeated ketamine administration did not cause any apparent impairment of spatial learning and memory in the water maze experiment conducted.?Conclusion Repeated administration of ketamine may impair learning and memory in early developing rats, but this kind of impairment is not exhibited in spatial learning and memory.