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小剂量MK-801对大鼠参照记忆、空间工作记忆和逆反学习能力的影响
  • 期刊名称:中国神经精神疾病杂志
  • 时间:0
  • 页码:261-265
  • 语言:中文
  • 分类:R749.3[医药卫生—神经病学与精神病学;医药卫生—临床医学]
  • 作者机构:[1]北京大学精神卫生研究所、卫生部精神卫生学重点实验室,北京100191
  • 相关基金:国家自然科学基金资助项目(编号:30770775 30800361)R749.
  • 相关项目:新生期阻断谷氨酸NMDA受体对大鼠感觉运动门控和NRG1-ErbB信号系统的影响
中文摘要:

目的 探讨腹腔注射N-甲基-D-天冬氨酸(NMDA)受体拮抗剂地卓西平马来酸盐(MK-801)对大鼠认知功能的影响。方法成年雄性SD大鼠随机分为MK-801组和对照组,分别腹腔注射小剂量生理盐水或MK-801(0.1 mg/kg)20 min后在Morris水迷宫中评定MK-801对大鼠参照记忆、空间工作记忆和逆反学习能力的影响。结果参照记忆任务中,与对照组相比MK-801组逃避潜伏期延长(P〈0.05),且在目标象限的探索时间百分比[(22.7±2.9)%]与相邻象限[(24.0±0.9)%]和对立象限[(29.3±2.4)%]的差异无统计学意义(P〉0.05);空间工作记忆任务中,对照组匹配试次潜伏期显著短于样本试次[(37.6±6.0)vs(61.5±6.3),P〈0.05],而MK-801组两试次潜伏期差异无统计学意义[(53.8±7.8)vs(62.2±7.1),P〉0.05];逆反学习任务中,与对照组相比MK-801组潜伏期明显延长(P〈0.05),且在空间探索中新旧目标象限探索时间百分比差值小于对照组[(-0.01±4.7)vs(23.5±6.2),P〈0.01]。结论腹腔注射小剂量MK-801破坏了大鼠的参照记忆、空间工作记忆和逆反学习,提示其在多个认知维度上可模拟精神分裂症患者的认知缺陷。

英文摘要:

Objective To investigate the effects of the N-methyl-D-aspartate(NMDA) receptor antagonist,dizocipline maleate(MK-801),on cognitive functions in rats.Methods Adult male Sprague-Dawley rats received an intraperitoneal injection of either low-dose MK-801(0.1 mg/kg) or saline and behavioral tests 20 min later.Reference memory,spatial working memory and reversal learning were tested using the Morris water maze.Results In the reference memory task,MK-801-treated animals showed significantly longer escaping latencies compared with controls(P0.05).In the probe test,MK-801-treated animals did not shown any difference between the target quadrant [(22.7±2.9)%] and other quadrants [(24.0±0.9)%,(29.3±2.4)%](P0.05).In the spatial working memory task,the latency of matching trials was significantly shorter than that of sample trials in the control group [(37.6±6.0) vs(61.5±6.3),P0.05)],whereas the MK-801 group didn't exhibit significant differences between these two trials [(53.8±7.8) vs(62.2±7.1),P0.05].In the reversal learning test,escaping latencies of MK-801 treated animals were significantly longer than those of the control group(P0.05).The comparison of the time spent in the target quadrant in the probe tests of the reference memory phase and the reversal learning phase revealed that the performance of the MK-801 group in reversal learning was significantly inferior to the control group [(-0.01±4.7) vs(23.5±6.2),P0.01].Conclusions Low-dose MK-801 can induce deficits in reference memory,spatial working memory and reversal learning in rats,thus being a potential animal model to mimic cognitive deficits of schizophrenia in several aspects.

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