氯胺酮对未成年大鼠学习能力和细胞外信号调节激酶的影响

目的研究氯胺酮对未成年大鼠学习记忆能力的影响,并观察其对海马神经元细胞外信号调节激酶(ERK)表达的影响。方法48只21日龄SD大鼠随机均分为六组,分别为空白对照组(C组)、训练组(T组)、氯胺酮注射后6、12、24和72h组(K6、K12、K24、K72组)。氯胺酮组大鼠予以50mg/kg氯胺酮腹腔注射,在各时间点用Y型迷宫测试各组大鼠的空间搜索和学习能力。训练组只接受Y迷宫测试。所有动物训练后即刻取大鼠海马行免疫组化染色,观察ERK1、ERK2和p-ERK1/2的表达。结果K6、K12、K24组大鼠的学习次数和总反应时间与T组比较差异有统计学意义(P<0.05)。免疫组化显示C组大鼠海马仅有极少量p-ERK1/2表达,而ERK1和ERK2有少许表达;所有接受迷宫测试大鼠的ERK1、ERK2和p-ERK1/2表达比C组均有显著增多(P<0.01)。K6、K12组大鼠海马ERK1、ERK2和p-ERK1/2的表达与T组相比差异有统计学意义(P<0.05)。结论单次注射50mg/kg氯胺酮可在短时间内损害21日龄SD大鼠的空间学习能力,而这个损害与海马ERK信号转导通路受到抑制有关。

Effect of ketamine on ERK expression in hippocampal neural cells and the ability of learning behavior in minor rats

Objective To study the effects of ketamine on ERK expression in hippocampal neural cells and the ability of learning behavior in minor rats.Methods Forty-eight Sprague-Dawley rats of 21 days old were randomly divided into 6 groups:empty control group(C),training group(T) and ketamine group.The ketamine group was subdivided into groups of 6 h(K6),12 h(K12),24 h(K24) and 72 h(K72) after injection.The rats in ketamine groups were intraperitoneally anesthetized with 50 mg/kg ketamine.The Y-maze was used to test the ability of learning and spatial localization on rats at 6,12,24,and 72 h.Group T only received light-electricity integrated training.At the end of training,all rats were killed and the ERK1,ERK2 and p-ERK1/2 were tested using immunhistochemistry.ResultsThe learning times and total reaction time(TRT) of K6,K12,K24 groups were significantly different from those of group T(P<0.05).The expression of p-ERK1/2 was little to be detected in the hippocampus of group C,while that of ERK1 and ERK2 was more.Immunohistochemical staining showed that the level of ERK1,ERK2 and p-ERK1/2 in all rats which received light-electricity integrated training increased remarkably compared with that in group C(P<0.01).The expression of ERK1,ERK2 and p-ERK1/2 in hippocampal neural cells of K6,K12 groups significantly decreased compared with that of group T(P<0.05).Conclusion Administration of ketamine 50 mg/kg may impair the learning ability of 21 days old rats in short term,and ERK signal transduction pathway may be involved in the impairment of ketamine.