Chang Jing-Yu, Shi Li-Hong, Luo Fei, Woodward Donald J
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Brain Res. 2003 Sep 5;983(1-2):174-84. doi: 10.1016/s0006-8993(03)03053-1.
This study investigated the influence of electrical stimulation of the subthalamic nucleus (STN) on motor impairment induced by unilateral 6-hydroxydopamine (6-OHDA) lesions in the medial forebrain bundle. Rats were trained to walk on a treadmill and then implanted with microelectrode arrays in and near the STN. The neurotoxin 6-OHDA was injected into the medial forebrain bundle (MFB) unilaterally to produce a targeted lesion of the dopaminergic system. Successful lesions produced impaired treadmill walking behavior. High frequency stimulation (HFS) of the STN improved treadmill walking immediately and restored normal walking patterns. The same HFS failed to evoke visible side effects such as stepping, turning, raising of the head or facial muscle contraction in the absence of treadmill movement, or to change rotational behaviors elicited by the dopamine (DA) agonist apomorphine in unilateral lesioned rats. This suggests that the stimulation did not cause movement by an activation of brainstem locomotor regions or an increase attention leading to movement. Apomorphine-induced rotation may represent an imbalance of dopaminergic activation which remains during HFS. This work may provide a rodent model for deep brain stimulation (DBS) in patients with Parkinson's disease, and be suitable for further investigation of the neural mechanisms underlying the therapeutic effects of DBS.
本研究调查了丘脑底核（STN）电刺激对内侧前脑束单侧6-羟基多巴胺（6-OHDA）损伤所致运动障碍的影响。将大鼠训练在跑步机上行走，然后在STN及其附近植入微电极阵列。将神经毒素6-OHDA单侧注入内侧前脑束（MFB）以产生多巴胺能系统的靶向损伤。成功的损伤导致跑步机行走行为受损。STN的高频刺激（HFS）立即改善了跑步机行走，并恢复了正常行走模式。在没有跑步机运动的情况下，相同的HFS未能引发可见的副作用，如踏步、转身、抬头或面部肌肉收缩，也未能改变单侧损伤大鼠中多巴胺（DA）激动剂阿扑吗啡引发的旋转行为。这表明该刺激不是通过激活脑干运动区域或增加导致运动的注意力来引起运动的。阿扑吗啡诱导的旋转可能代表多巴胺能激活的失衡，这种失衡在HFS期间仍然存在。这项工作可能为帕金森病患者的深部脑刺激（DBS）提供一种啮齿动物模型，并适合进一步研究DBS治疗效果背后的神经机制。
