The effect of additional noradrenergic and serotonergic depletion on a lateralised choice reaction time task in rats with nigral 6-OHDA lesions
The effect of additional noradrenergic and serotonergic depletion on a lateralised choice reaction time task in rats with nigral 6-OHDA lesions
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DOI：
10.1016/j.expneurol.2013.11.015
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发表时间：
2014-03-01
影响因子：
5.3
通讯作者：
Dunnett, Stephen B.
中科院分区：
文献类型：
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作者：
Lindgren, Hanna S.;Demirbugen, Merve;Dunnett, Stephen B.
帕金森病 (PD) 患者经常患有视觉空间缺陷，这被认为是外部空间表征的破坏。侧化选择反应时间（CRT）任务是啮齿类动物的一项操作性任务，可以评估类似的缺陷。已经证明，单侧注射 6-羟基多巴胺 (6-OHDA) 后，此任务中的特定参数会受到干扰，这与此类病变不可避免地发生的多巴胺 (DA) 消耗有关。然而，研究表明，这种类型的病变也会影响血清素能（5HT）和去甲肾上腺素能（NA）系统。然而，这些系统对 CRT 任务中参数的影响尚未得到研究。 为此，在接受 DAergic 系统的选择性损伤之前，对大鼠进行 CRT 任务的预训练，无论是单独损伤还是与 NA 或 5HT 系统的消耗联合损伤。与病变对侧的假病变对照相比，所有具有 6-OHDA 病变的大鼠在侧向运动的选择、启动和执行方面均表现出逐渐下降。他们还显示可用试验数量减少以及程序错误数量增加。有趣的是，与具有 6-OHDA 损伤的其他两组相比，在整个测试期间，具有额外去甲肾上腺素能损伤的组对侧化刺激的反应明显较慢。然而，在任务中评估的其他参数中，三个不同病变组之间没有差异。这些数据证实了先前的发现，表明侧化 CRT 任务中评估的大多数参数强烈依赖于 DA。然而，这项研究还表明，NAergic 系统可能在影响注意力表现方面发挥重要作用，影响对所呈现的侧化刺激的反应能力。 (C) 2013 Elsevier Inc. 保留所有权利。
Parkinson's disease (PD) patients often suffer from visuospatial deficits, which have been considered a disruption of the representation of external space. The lateralised choice reaction time (CRT) task is an operant task for rodents in which similar deficits can be assessed. It has been demonstrated that specific parameters in this task is disrupted after unilateral injections of 6-hydroxydopamine (6-OHDA), which have been associated with the dopamine (DA) depletion that inevitably follows this type of lesion. However, studies have demonstrated that this type of lesion also affects the serotonergic (5HT) and noradrenergic (NA) systems. However, the impact of these systems on parameters in the CRT task had not yet been investigated.To this end, rats were pretrained on the CRT task before receiving selective lesions of the DAergic system, either alone or in combination with depletion of the NA or 5HT system. All rats with a 6-OHDA lesion displayed a gradual decline in the selection, initiation and execution of lateralised movements compared to sham-lesion controls on the side contralateral to the lesion. They also displayed a reduced number of useable trials as well as an increased number of procedural errors. Interestingly, the group with an additional noradrenergic lesion was significantly slower in reacting to lateralised stimuli throughout the testing period compared to the other two groups with a 6-OHDA lesion. There was however no difference between the three different lesion groups in the other parameters assessed in the task.These data confirm previous findings demonstrating that the majority of the parameters assessed in the lateralised CRT task are strongly dependent on DA However, this study has also shown that the NAergic system may play an important role in contributing to the attentive performance influencing the capacity to react to the presented lateralised stimuli. (C) 2013 Elsevier Inc. All rights reserved.