Lindgren Hanna S, Klein Alexander, Dunnett Stephen B
Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK.
Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK.
Behav Brain Res. 2014 Jun 1;266:207-15. doi: 10.1016/j.bbr.2014.02.043. Epub 2014 Mar 5.
Unilateral intrastriatal and intra-medial forebrain bundle injections of 6-OHDA impair the performance in a lateralised choice reaction time task. However, the extent and pattern of deficits after nigral 6-OHDA injections is less well studied, as well as the impact of training regime or the modification of various task parameters. The nigral 6-OHDA lesion resulted in impaired response accuracy and an increased time to react to and execute the response on the side contralateral to the lesion as compared to sham-lesioned controls. Pre-training of the rats on the task prior to the lesion resulted in slightly faster reaction times as well as a reduced number of preservative panel presses compared to when rats were trained after the 6-OHDA injection. When the rat had to perform a longer sustained nose poke before responding to the lateralised stimuli, the number of useable trials was reduced in both controls and 6-OHDA rats as a result of an increased number of premature withdrawals from the centre hole. This study demonstrates that rats with a nigral 6-OHDA lesion display several distinct deficits in this operant task, which are similar to those seen after striatal and bundle 6-OHDA injections. In addition, by combining pre-training with the use of a short set of holds, improved sensitivity of this task can be achieved. This improvement in sensitivity may be of advantage when exploring new therapeutic interventions for PD, where subtle but relevant changes in performance may arise.
单侧纹状体内和内侧前脑束注射6-羟基多巴胺(6-OHDA)会损害在侧化选择反应时任务中的表现。然而,黑质注射6-OHDA后的缺陷程度和模式研究较少,训练方案或各种任务参数的改变所产生的影响也研究较少。与假损伤对照组相比,黑质6-OHDA损伤导致反应准确性受损,且对损伤对侧的反应做出反应并执行该反应的时间增加。与6-OHDA注射后训练大鼠相比,在损伤前对大鼠进行该任务的预训练会使反应时间略快,且保持面板按压的次数减少。当大鼠在对侧化刺激做出反应之前必须进行更长时间的持续鼻触时,由于从中心孔过早退出的次数增加,对照组和6-OHDA大鼠的可用试验次数均减少。本研究表明,黑质6-OHDA损伤的大鼠在该操作性任务中表现出几种明显的缺陷,这与纹状体和束注射6-OHDA后所见的缺陷相似。此外,通过将预训练与使用短时间的保持相结合,可以提高该任务的敏感性。当探索帕金森病的新治疗干预措施时,这种敏感性的提高可能具有优势,因为在这些干预措施中可能会出现细微但相关的性能变化。