Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice
Bimodal effects of MK-801 on locomotion and stereotypy in C57BL/6 mice
复制标题
DOI：
10.1007/s00213-004-1944-1
复制
发表时间：
2005-01-01
影响因子：
3.4
通讯作者：
Yu, L
中科院分区：
文献类型：
--
作者：
Wu, JH;Zou, H;Yu, L
基本原理：全身注射非竞争性NMDA（N-甲基-D-天冬氨酸）受体拮抗剂MK-801（马来酸地佐环平）可引起啮齿动物运动增加和各种刻板行为，这些行为被提议用于模拟人类精神分裂症症状的某些方面。目的：本研究全面表征了MK-801对C57 BL/6小鼠品系（一种常用于转基因小鼠的品系）运动和刻板行为的双峰效应。结果如下：我们发现，重要的是要同时分析运动和刻板印象，因为MK-801诱导的刻板印象会导致异常运动，这些运动被自动光束检测系统记录为运动。此外，重要的是要分析MK-801在延长的时间跨度内的双峰效应，而不是通常使用的较窄时间窗，如在较高剂量下（例如，例如，在一个实施例中，高于0.3 mg/kg），只有在刻板阶段消退后才出现过度运动阶段。我们还观察到，表观剂量-反应曲线对选择用于分析的特定时间窗口非常敏感，因为MK-801影响刺激运动的时间过程和最大值。我们表明，分析每只动物诱导的运动绝对峰值，而不是组平均时间过程，提供了一种在更宽范围的MK-801剂量下敏感的测量方法。有趣的是，MK-801即使在0.02 mg/kg的非常低的剂量下也抑制而不是增强了直立行为，在这方面与安非他明不同。结论：非竞争性NMDA受体拮抗剂MK-801在小鼠中诱导了一种复杂的行为改变模式，涉及行为变化的时间过程和剂量-反应关系。本研究结果为MK-801诱导小鼠行为研究的兴趣日益增长提供了基础和参考框架。
Rationale: Systemic injection of the noncompetitive NMDA (N-methyl-D-aspartate) receptor antagonist MK-801 ( dizocilpine maleate) causes both increased locomotion in rodents and various stereotypic behaviors that are proposed to model certain aspects of schizophrenic symptoms in humans. Objectives: This study presents a comprehensive characterization of the bimodal effects of MK-801 on locomotion and stereotypy in the C57BL/6 mouse strain, a strain commonly used for genetically modified mice. Results: We found that it is important to analyze both locomotion and stereotypy in parallel, as MK-801-induced stereotypy results in abnormal movements that are recorded as locomotion by automated beam detection systems. Furthermore, it is important to analyze the bimodal effects of MK-801 over an extended time span, rather than the commonly used narrower time window, as at higher doses ( e. g., above 0.3 mg/kg) the hyperlocomotion phase develops only after the stereotypic phase subsides. We also observed that the apparent dose - response curve is very sensitive to the particular time window chosen for analysis because MK-801 affects both the time course and maximum value of stimulated locomotion. We show that analyzing the absolute peak value of locomotion induced for each animal, rather than group-averaged time courses, provides a measure that is sensitive over a wider range of MK-801 doses. Interestingly, MK-801 even at a very low dose of 0.02 mg/kg suppressed rather than enhanced rearing behavior, differing in this regard from amphetamine. Conclusions: The non-competitive NMDA receptor antagonist MK-801 induces a complex pattern of behavioral modification in mice with respect to both the time course and the dose - response relationship of behavioral changes. The results of this study provide a foundation and frame of reference for the growing interest in studying MK-801-induced behavior in mice.