Université Bordeaux Segalen, Centre National de la Recherche Scientifique (CNRS UMR 5293), Neurodegenerative Diseases Institute, Group Monoamines, DBS and Parkinson's disease, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France.
Neurobiol Dis. 2012 Feb;45(2):763-73. doi: 10.1016/j.nbd.2011.10.023. Epub 2011 Nov 4.
The loss of dopamine (DA) neurons has been the pathophysiological focus of the devastating conditions of Parkinson's disease, but depletion of DA alone in animal models has failed to simultaneously elicit both the motor and non-motor deficits of PD. The present study aimed to investigate, in rats, the respective role of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) depletions on motor and non-motor behaviors and on subthalamic (STN) neuronal activity. We show that NA or DA depletion significantly decreased locomotor activity and enhanced the proportion of bursty and irregular STN neurons. Anxiety-like states required DA depletion plus the depletion of 5-HT or NA. Anhedonia and "depressive-like" behavior emerged only from the combined depletion of all three monoamines, an effect paralleled by an increase in the firing rate and the proportion of bursty and irregular STN neurons. Here, we provide evidence for the exacerbation of behavioral deficits when NA and/or 5-HT depletions are combined with DA depletion, bringing new insight into the combined roles of the three monoamines in PD.
多巴胺（DA）神经元的丧失一直是帕金森病等破坏性疾病的病理生理学焦点，但在动物模型中单独耗尽 DA 未能同时引起 PD 的运动和非运动缺陷。本研究旨在研究大鼠中多巴胺（DA）、去甲肾上腺素（NA）和 5-羟色胺（5-HT）耗竭对运动和非运动行为以及丘脑底核（STN）神经元活动的各自作用。我们表明，NA 或 DA 耗竭显着降低了运动活性并增强了 STN 神经元爆发和不规则的比例。焦虑样状态需要 DA 耗竭加上 5-HT 或 NA 的耗竭。快感缺失和“抑郁样”行为仅在所有三种单胺类物质联合耗竭时出现，这种效应伴随着 STN 神经元的放电率和爆发性和不规则性比例的增加。在这里，我们提供了证据表明，当 NA 和/或 5-HT 耗竭与 DA 耗竭结合时，行为缺陷会加剧，这为三种单胺类物质在 PD 中的联合作用提供了新的见解。
