在6-羟基多巴胺诱导的帕金森病大鼠中，自发运动活性与左旋多巴诱发的运动障碍并无关联。
Spontaneous locomotor activity and L-DOPA-induced dyskinesia are not linked in 6-OHDA parkinsonian rats.
作者信息
Sgroi Stefania, Kaelin-Lang Alain, Capper-Loup Christine
机构信息
Department of Neurology and Department of Clinical Research, Movement Disorders Center, Inselspital, Bern University Hospital, and University of Bern Bern, Switzerland ; Graduate School for Cellular and Biomedical Sciences, University of Bern Bern, Switzerland ; Neurocentre of Southern Switzerland Lugano, Switzerland.
Department of Neurology and Department of Clinical Research, Movement Disorders Center, Inselspital, Bern University Hospital, and University of Bern Bern, Switzerland ; Neurocentre of Southern Switzerland Lugano, Switzerland.
出版信息
Front Behav Neurosci. 2014 Oct 2;8:331. doi: 10.3389/fnbeh.2014.00331. eCollection 2014.
Bradykinesia (slowness of movement) and other characteristic motor manifestations of Parkinson's disease (PD) are alleviated by treatment with L-dihydroxyphenylalanine (L-DOPA). Long-term L-DOPA treatment, however, is associated with complications such as motor fluctuations and dyskinesia that severely impair the quality of life. It is unclear whether the effect of L-DOPA on spontaneous motor activity and its dyskinesia-inducing effect share a common mechanism. To investigate the possible connection between these two effects, we analyzed the spontaneous locomotor activity of parkinsonian rats before surgery (unilateral injection of 6-OHDA in the right medial forebrain bundle), before treatment with L-DOPA, during L-DOPA treatment (the "ON" phase), and after the end of L-DOPA treatment (the "OFF" phase). We correlated the severity of dyskinesia (AIM scores) with locomotor responses in the ON/OFF phases of chronic L-DOPA treatment at two different doses. We treated three groups of parkinsonian animals with chronic injections of 8 mg/kg L-DOPA, 6 mg/kg L-DOPA, and saline solution and one group of non-lesioned animals with 8 mg/kg L-DOPA. At the end of the experiment, tyrosine hydroxylase (TH) immunoreactivity was analyzed in the striatum of all parkinsonian rats. We found no correlation between the severity of dyskinesia and spontaneous locomotor activity in the ON or OFF phase of L-DOPA treatment. The only observed correlation was between the pathological rotation induced by L-DOPA at the highest dose and locomotor activity in the ON phase of L-DOPA treatment. In addition, a L-DOPA withdrawal effect was observed, with worse motor performance in the OFF phase than before the start of L-DOPA treatment. These findings suggest that different neural mechanisms underlie the effect of L-DOPA on spontaneous motor activity and its dyskinesia-inducing effect, with a different dose-response relationship for each of these two effects.
帕金森病（PD）的运动迟缓（动作缓慢）及其他典型运动表现可通过左旋多巴（L - 二羟基苯丙氨酸，L - DOPA）治疗得到缓解。然而，长期使用L - DOPA治疗会引发诸如运动波动和异动症等并发症，严重影响生活质量。L - DOPA对自发运动活动的影响及其诱发异动症的作用是否具有共同机制尚不清楚。为了探究这两种效应之间的可能联系，我们分析了帕金森病大鼠在手术前（右侧内侧前脑束单侧注射6 - 羟基多巴胺）、L - DOPA治疗前、L - DOPA治疗期间（“开”期）以及L - DOPA治疗结束后（“关”期）的自发运动活动。我们将异动症的严重程度（异动症评分）与两种不同剂量的慢性L - DOPA治疗开/关期的运动反应进行了关联分析。我们用8 mg/kg L - DOPA、6 mg/kg L - DOPA和生理盐水对三组帕金森病动物进行了慢性注射治疗，并用8 mg/kg L - DOPA对一组未损伤动物进行了治疗。实验结束时，对所有帕金森病大鼠的纹状体进行了酪氨酸羟化酶（TH）免疫反应性分析。我们发现，在L - DOPA治疗的开期或关期，异动症严重程度与自发运动活动之间没有相关性。唯一观察到的相关性是最高剂量的L - DOPA诱导的病理性旋转与L - DOPA治疗开期的运动活动之间的相关性。此外，还观察到了L - DOPA撤药效应，即关期的运动表现比L - DOPA治疗开始前更差。这些发现表明，L - DOPA对自发运动活动的影响及其诱发异动症的作用基于不同的神经机制，且这两种效应各自具有不同的剂量 - 反应关系。
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