不同剂量甲基苯丙胺对小鼠空间学习记忆能力的影响及其机制  

Effects of different doses of methamphetamine on spatial learning and memory in mice and the mechanism

作　　者：曹国芬[1,2] 张永爱 张苏梅[1] 张海苗[1] 朱莉[2] 朱杰 周小兰 陈腾[2] CAO Guo-fen;ZHANG Yong-ai;ZHANG Su-mei;ZHANG Hai-miao;ZHU Li;ZHU Jie;ZHOU Xiao-lan;CHEN Teng(School of Nursing,Xi'an Medical College,Xi'an 710021;College of Forensic Medicine,Xi'an Jiaotong University Health Science Center,Xi'an 710061,China)

机构地区：[1]西安医学院护理学院,陕西西安710021 [2]西安交通大学医学部法医学院,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2019年第4期559-563,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金项目(No.81772034,81701870);陕西省教育厅专项科研计划项目(No.17JK0657);陕西省卫生计生科研基金项目(No.2016 A005);西安医学院护理学省级重点学科建设项目(No.16hlxk16)~~

摘　　要：目的研究不同剂量甲基苯丙胺(methamphetamine,METH)对小鼠空间学习记忆的影响及可能机制。方法以C57BL/6小鼠为研究对象,采用0.5、1.0、2.0 mg/kg的METH或生理盐水,在每天的Morris水迷宫行为学习前腹腔注射给药,连续5 d,每天4轮的定位航行实验训练,最后一次训练完24 h后进行空间探索实验,观察不同剂量METH对小鼠空间学习记忆的影响。测试后立即采用颈椎脱臼法处死小鼠,并剥离海马组织,采用Western blot方法检测海马中ERK1/2(extracellular signal-regulated kinase)、CREB(cAMP response element-binding protein)磷酸化水平的变化。结果相比盐水组小鼠,1.0 mg/kg METH组小鼠爬台潜伏期明显缩短( P <0.05),在目标象限的停留时间( P <0.05)、穿台次数( P <0.05)明显增加;0.5、2.0 mg/kg METH对小鼠空间学习记忆无明显影响,但是0.5 mg/kg METH组小鼠呈现记忆促进趋势,而2.0 mg/kg METH组小鼠呈现记忆破坏趋势;1.0 mg/kg METH组小鼠明显伴随海马中p-ERK1/2( P <0.05)、p-CREB( P <0.05)水平的增高。结论 1.0 mg/kg METH明显提高小鼠空间学习能力及记忆水平;在0.5、1.0、2.0 mg/kg的METH三个剂量之间,METH的效应呈倒U曲线型;海马中ERK1/2、CREB可能参与METH诱导的小鼠空间学习记忆的提高。Objective To investigate the different-dose effects of methamphetamine(METH) on spatial learning and memory and the possible mechanisms. Methods C57 BL/6 mice were treated with 0.5, 1.0 and 2.0 mg/kg of METH or normal saline. The drug was injected intraperitoneally 30 min prior to the Morris water maze. All mice experienced 5 consecutive days’ positioning navigation experiment and the spatial exploration experiment conducted 24 hours after the last training trial. Immediately after the probe test, the mice were killed by cervical dislocation and the hippocampus was dissected. Western blot was used to detect changes in phosphorylation levels of extracellular signal-regulated kinase(ERK1/2) and cAMP response element-binding protein(CREB) in the hippocampus. Results Compared with the mice in saline group, those in 1.0 mg/kg METH group had a significantly shorter latency(P<0.05), spent more time in the target quadrant(P<0.05), and had more platform site crossings(P<0.05).Moreover,0.5 and 2.0 mg/kg of METH did not significantly affect the mice's spatial learning and memory,but 0.5 mg/kg of METH showed a memory-promoting trend,while 2.0 mg/kg of METH showed a memory-destroying trend.METH of 1.0 mg/kg significantly increased p-ERK1/2(P<0.05)and p-CREB(P<0.05)levels in the hippocampus.Conclusion METH of 1.0 mg/kg significantly improved mice's spatial learning and memory.The effect of METH is an inverted U-curve among three doses of METH at 0.5,1.0 and2.0 mg/kg.ERK1/2 and CREB in the hippocampus may be involved in METH-induced improvement of spatial learning and memory in mice.

关 键 词：甲基苯丙胺 空间学习 空间记忆 海马 ERK1/2 CREB 

分 类 号：R89[医药卫生—法医学]