Univ. de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, 33076 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33076 Bordeaux, France.
Department of Neuroscience and Neurosurgery, Maastricht University Medical Center, Maastricht, The Netherlands.
Neurobiol Dis. 2018 Feb;110:20-28. doi: 10.1016/j.nbd.2017.11.001. Epub 2017 Nov 3.
Anxiety in Parkinson's disease is a comorbid non-motor symptom that alters the quality of life of patients. Its neuronal substrates and those of l-Dopa treatment are still poorly known. Using different combinations of monoaminergic system lesions in the rat, we addressed the contribution of these systems in the efficacy of l-DOPA on anxiety and on the neuronal activity of basolateral amygdala (BLA), a brain structure involved in anxiety. Anxiety, locomotor activity and motor performance were assessed using the elevated plus maze, the open field and the skinner box, respectively. The neuronal activity of BLA was electrophysiologically recorded and the loss of dopamine, noradrenaline and serotonin neurons was quantified by immunohistochemistry and stereology. Selective bilateral lesion of dopamine neurons, with or without the additional lesions of noradrenaline and/or serotonin neurons, induced anxiety disorder. l-Dopa significantly decreased anxiety in animals with bilateral lesion of dopamine neurons alone or combined with that of noradrenaline neurons. In these two groups, l-DOPA enhanced the firing rate of BLA neurons. However, in animals with combined lesions of dopamine and serotonin neurons or in animals with lesions of the three monoaminergic systems, l-Dopa was no longer able to decrease anxiety behavior or to change the electrophysiological parameters of BLA neurons. Our data provide the first evidence of the key and positive role of the serotonergic system in the combined efficacy of l-Dopa on anxiety and the paralleled BLA neuronal activity, suggesting that the enhancement of the activity of serotonin neurons may boost the anxiolytic action of l-DOPA.
帕金森病中的焦虑是一种共病性的非运动症状，会改变患者的生活质量。其神经元基础和左旋多巴治疗的基础仍知之甚少。我们使用大鼠单胺能系统损伤的不同组合，研究了这些系统对左旋多巴治疗焦虑和基底外侧杏仁核（BLA）神经元活动的疗效的贡献，BLA 是参与焦虑的大脑结构。使用高架十字迷宫、旷场和斯金纳箱分别评估焦虑、运动活动和运动表现。通过免疫组织化学和体视学定量来测量 BLA 的神经元活性和多巴胺、去甲肾上腺素和 5-羟色胺神经元的丢失。选择性双侧多巴胺神经元损伤，无论是否伴有去甲肾上腺素和/或 5-羟色胺神经元的额外损伤，都会导致焦虑障碍。左旋多巴可显著降低仅双侧多巴胺神经元损伤或与去甲肾上腺素神经元损伤结合的动物的焦虑。在这两组动物中，左旋多巴增强了 BLA 神经元的放电率。然而，在多巴胺和 5-羟色胺神经元联合损伤的动物或在三种单胺能系统损伤的动物中，左旋多巴不再能够降低焦虑行为或改变 BLA 神经元的电生理参数。我们的数据首次提供了证据，证明 5-羟色胺系统在左旋多巴联合治疗焦虑和 BLA 神经元活动中的关键和积极作用，表明增强 5-羟色胺神经元的活性可能增强左旋多巴的抗焦虑作用。
