Involvement of ventrolateral striatal dopamine in movement initiation and execution: A microdialysis and behavioral investigation
Involvement of ventrolateral striatal dopamine in movement initiation and execution: A microdialysis and behavioral investigation
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DOI：
10.1016/0306-4522(95)00407-6
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发表时间：
1996-02-01
期刊：
影响因子：
3.3
通讯作者：
Salamone, JD
中科院分区：
文献类型：
--
作者：
Cousins, MS;Salamone, JD
先前的研究表明，大鼠新纹状体的腹外侧区域是多巴胺消耗产生严重运动缺陷的部位，影响食物处理和杠杆按压。在本工作中，进行了两个实验来研究腹外侧纹状体多巴胺在杠杆按压中的作用。第一个实验详细描述了向腹侧纹状体注射神经毒性药物6-羟多巴胺引起的运动损伤。按固定比率5按杠杆时的行为输出由计算机系统记录，该系统测量每次按杠杆的持续时间和反应启动时间。响应起始时间定义为从一次杠杆按压偏移到下一次按压开始的时间。6-羟多巴胺注射引起的多巴胺消耗严重抑制了杠杆按压反应状态。这一缺陷主要是由于平均响应启动时间的急剧增加。对反应启动时间分布的分析表明，多巴胺耗尽大鼠在快速启动时间（如0-125 ms）下的反应相对较少，并且多巴胺耗尽导致反应暂停次数急剧增加（即反应启动时间大于2.5 s）。这种开始运动的缓慢对多巴胺消耗的影响非常敏感，即使是轻度多巴胺消耗（对照组水平的29.1%）的动物也表现出增加的开始时间。对反应持续时间的分析表明，多巴胺耗竭导致持续时间分布的变化，使耗竭大鼠的模态反应持续时间为375-500 ms，而对照模式为125-250 ms。在多巴胺消耗较严重的动物中，平均反应持续时间总体上有所增加，而中度多巴胺消耗的大鼠的平均反应持续时间没有变化。实验二采用体内透析法研究杠杆按压时腹外侧纹状体多巴胺的动态活性。在30分钟的固定比率5杠杆按压过程中，多巴胺释放量虽小但显著增加（比基线高20.9%）。杠杆按压率与多巴胺释放增加之间没有线性或曲线相关性。在杠杆按压过程中，腹侧纹状体多巴胺释放量的相对适度增加以及多巴胺释放与行为输出之间缺乏相关性，可能表明在杠杆按压过程中，腹侧纹状体多巴胺主要起放任作用。这些结果表明，大鼠腹外侧纹状体多巴胺消耗产生的熟练运动控制缺陷与帕金森病患者观察到的运动缺陷相似。
Previous studies have demonstrated that the ventrolateral region of the rat neostriatum is the site at which dopamine depletions produce profound motor deficits that interfere with food handling and lever pressing. In the present work, two experiments were undertaken to investigate the role of ventrolateral striatal dopamine in lever pressing. The first experiment was a detailed characterization of the motor impairments induced by injections of the neurotoxic agent 6-hydroxydopamine into the ventrolateral striatum. Behavioral output during lever pressing on a fixed ratio 5 schedule was recorded by a computerized system that measured the duration and response initiation time for each lever press. Response initiation time was defined as the time from offset of one lever press to the onset of the next one. Dopamine depletions resulting from 6-hydroxydopamine injections profoundly depressed lever pressing response tate. This deficit was largely due to a dramatic increase in the average response initiation time. Analysis of the distribution of response initiation times indicated that dopamine-depleted rats made relatively few responses with fast initiation times (e.g. 0-125 ms), and also that dopamine depletions led to a dramatic increase in the number of pauses in responding (i.e. response initiation times greater than 2.5 s). This slowing of the initiation of movement was very sensitive to the effects of dopamine depletions, and even animals with mild dopamine depletions (29.1% of control levels) showed increased initiation times. Analysis of response durations indicated that dopamine depletions resulted in a shift in the distribution of durations such that depleted rats had a modal response duration of 375-500 ms, in contrast to the control mode of 125-250 ms. There was an overall increase in average response duration among animals with more severe dopamine depletions, although rats with moderate depletions showed no change in average response duration. In the second experiment, in vivo dialysis methods were used to study the dynamic activity of ventrolateral striatal dopamine during lever pressing. During the performance of a 30-min fixed ratio 5 lever pressing session, there was a small but significant increase (20.9% above baseline) in dopamine release. There was not a linear or curvilinear correlation between lever pressing rate and increases in dopamine release. The relatively modest increase in ventrolateral striatal dopamine release during lever pressing and the lack of relation between dopamine release and behavioral output may indicate that dopamine in the ventrolateral striatum plays mainly a permissive role in lever pressing.These results suggest that ventrolateral striatal dopamine depletions in rats produce deficits in skilled motor control that are similar to the motor deficits observed in patients with Parkinson's disease.