Division of Neurology, Toronto Western Research Institute, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.
Can J Neurol Sci. 2010 Jan;37(1):86-95. doi: 10.1017/s0317167100009707.
Neuropsychiatric symptoms are increasingly recognised as a significant problem in patients with Parkinson's disease (PD). These symptoms may be due to 'sensitisation' following repeated levodopa treatment or a direct effect of dopamine on the disease state. The levodopa-treated MPTP-lesioned marmoset was used as a model of neuropsychiatric symptoms in PD patients. Here we compare the time course of levodopa-induced motor fluctuations and neuropsychiatric-like behaviors to determine the relationship between duration of treatment and onset of symptoms.
Marmosets were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2.0 mg/kg s.c.) for five days, resulting in stable parkinsonism. Levodopa (15 mg/kg and benserazide, 3.75 mg/kg) p.o. b.i.d, was administered for 30 days. Animals were evaluated for parkinsonian disability, dyskinesia and on-time (motor fluctuations) and neuropsychiatric-like behaviors on Day 0 (prior to levodopa) and on Days 1, 7, 13, 27 and 30 of treatment using post hoc DVD analysis by a trained rater, blind to the treatment day.
The neuropsychiatric-like behavior rating scale demonstrated high interrater reliability between three trained raters of differing professional backgrounds. As anticipated, animals exhibited a progressive increase in levodopa-induced motor fluctuations, dyskinesia and wearing-off, that correlated with the duration of levodopa therapy. In contrast, levodopa-induced neuropsychiatric-like behaviors were present on Day 1 of levodopa treatment and their severity did not correlate with duration of treatment.
The data suggest that neuropsychiatric disorders in PD are more likely an interaction between levodopa and the disease state than a consequence of sensitisation to repeated dopaminergic therapy.
神经精神症状在帕金森病（PD）患者中日益被认为是一个重大问题。这些症状可能是由于重复左旋多巴治疗后的“敏化”，或是多巴胺对疾病状态的直接影响所致。已将经左旋多巴治疗的 MPTP 损伤的狨猴用作 PD 患者神经精神症状的模型。在这里，我们比较了左旋多巴引起的运动波动和神经精神样行为的时间过程，以确定治疗持续时间与症状发作之间的关系。
对狨猴连续五天皮下注射 1-甲基-4-苯基-1,2,3,6-四氢吡啶（2.0mg/kg），导致稳定的帕金森病。每天口服左旋多巴（15mg/kg 和苄丝肼，3.75mg/kg）两次，共 30 天。在治疗的第 0 天（在给予左旋多巴之前）和第 1、7、13、27 和 30 天，通过训练有素的评分员使用事后 DVD 分析，根据不同的专业背景对三名评分员进行了帕金森病残疾、运动障碍和按时（运动波动）和神经精神样行为的评估。
神经精神样行为评定量表显示，三名不同专业背景的训练有素评分员之间具有很高的组内信度。正如预期的那样，动物表现出左旋多巴诱导的运动波动、运动障碍和“开-关”现象逐渐增加，这与左旋多巴治疗的持续时间相关。相比之下，在左旋多巴治疗的第 1 天就出现了左旋多巴诱导的神经精神样行为，其严重程度与治疗持续时间无关。
数据表明，PD 中的神经精神障碍更可能是左旋多巴与疾病状态相互作用的结果，而不是对重复多巴胺治疗产生敏化的结果。
