Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat
Comparison of rating scales used to evaluate L-DOPA-induced dyskinesia in the 6-OHDA lesioned rat
复制标题
DOI：
10.1016/j.nbd.2012.10.013
复制
发表时间：
2013-02-01
影响因子：
6.1
通讯作者：
Lane, Emma L.
中科院分区：
文献类型：
--
作者：
Breger, Ludivine S.;Dunnett, Stephen B.;Lane, Emma L.
异常不自主运动 (AIM) 评定量表经常用于研究 6-OHDA 损伤啮齿动物中 L-DOPA 诱发的运动障碍 (LID) 的机制以及帕金森病新疗法诱发或减轻类似异常行为的倾向。尽管存在至少一种经过充分验证的方法，但其他 AIM 量表也在使用中。此外，原始量表及其使用方法已经有了发展和变化，但没有重新验证。在这项研究中，6-OHDA 内侧前脑束损伤的 Sprague-Dawley 大鼠接受慢性 L-DOPA 6 mg/kg/天治疗 5 周，然后再接受 12 mg/kg/天治疗 5 周。注射左旋多巴后 3 小时内，每周对大鼠进行四个已发表的 AIM 和刻板印象量表的同步评级，同时记录旋转情况。然后，使用已知可在临床和灵长类动物中减少 LID（金刚烷胺）或干扰 L-DOPA（D-1 和 D-2 多巴胺受体拮抗剂、SCH-23390 和雷氯必利）活性的药物，对三种当代 AIM 量表进行药理学验证。我们还证明，AIM、刻板行为和旋转行为是慢性和急性左旋多巴治疗引起的不同运动功能障碍，应单独评估。在多个时间点进行评估至关重要，尤其是在测试新的潜在抗运动障碍治疗的功效时。对于所有 AIM 和旋转测试来说，最重要的是对所使用的秤和所使用的环境进行内部验证。 (C) 2012 Elsevier Inc. 保留所有权利。
Abnormal involuntary movement (AIM) rating scales are frequently used to study the mechanisms underlying L-DOPA-induced dyskinesia (LID) in 6-OHDA lesioned rodents and the propensity of novel treatments for Parkinson's disease to induce or alleviate similar abnormal behaviours. Despite the existence of at least one well validated method, other AIM scales are also in use. Moreover, there have been developments and variations in the original scales and their methods of use, without re-validation. In this study, 6-OHDA medial forebrain bundle lesioned Sprague-Dawley rats were treated with chronic L-DOPA 6 mg/kg/day for 5 weeks followed by 12 mg/kg/day for another 5 weeks. Rats were assessed weekly by simultaneous ratings on four published AIM and stereotypy scales with concurrent recording of rotation, over 3 hours following L-DOPA injection. Three contemporary AIM scales have then been validated pharmacologically using agents that are known to reduce LID clinically and in primates (amantadine) or to interfere with the activity of L-DOPA (the D-1 and D-2 dopamine receptor antagonists, SCH-23390 and raclopride) respectively. We also demonstrate that AIM, stereotypic and rotational behaviour are distinct motor dysfunctions induced by chronic and acute treatment of L-DOPA, and should be assessed separately. The undertaking of assessments at multiple time points is essential especially when testing the efficacy of new potential anti-dyskinetic treatments. Importantly critical to all AIM and rotation testing is the internal validation of both the scale being used and the environment being used. (C) 2012 Elsevier Inc. All rights reserved.