COMPLEX DEFICITS ON REACTION-TIME PERFORMANCE FOLLOWING BILATERAL INTRASTRIATAL 6-OHDA INFUSION IN THE RAT
COMPLEX DEFICITS ON REACTION-TIME PERFORMANCE FOLLOWING BILATERAL INTRASTRIATAL 6-OHDA INFUSION IN THE RAT
复制标题
DOI：
10.1111/j.1460-9568.1995.tb01085.x
复制
发表时间：
1995-05-01
影响因子：
3.4
通讯作者：
DASZUTA, A
中科院分区：
文献类型：
--
作者：
AMALRIC, M;MOUKHLES, H;DASZUTA, A
本研究探讨了能力的大鼠进行双边6-羟基多巴胺病变的终端区的黑质纹状体多巴胺系统执行prelearned反应时间任务。这种损伤模型，诱导纹状体的部分多巴胺去神经支配（多巴胺纹状体组织含量的74%耗尽），伴随黑质中多巴胺细胞体的逆行变性，保留中脑边缘多巴胺能通路，非常接近在人类特发性帕金森病中观察到的神经元变性。大鼠预先训练释放杠杆，在反应时间限制内，通过食物颗粒强化视觉提示后，光刺激的开始随机变化后，不可预测的延迟期为0.25 - 1.0秒，多巴胺能损伤的大鼠表现出中度至广泛的性能缺陷，术后5周未得到补偿。超过一半的病变动物（64%）表现出严重的缺陷，其特征是预期的数量同时增加（在视觉提示之前过早释放杠杆）和延迟反应（在反应时间限制之后释放杠杆）在某些情况下具有缩短的反应时间，比例较小（36%）的损伤动物表现出轻度的表现障碍，延迟反应大幅增加，反应时间延长，但没有改变的数量，预期的反应。不对称损伤对反应时间性能没有影响。酪氨酸羟化酶免疫染色的检查显示，在最受损的动物多巴胺耗竭是广泛的内侧纹状体，而它仅限于背外侧纹状体受损最少的动物。结果表明，纹状体水平的多巴胺功能的减少严重破坏了条件反应时间任务的性能。背外侧纹状体中的部分多巴胺耗竭诱导运动启动缺陷（即仅增加延迟反应），较大的纹状体多巴胺耗竭可能产生运动和认知缺陷（对反应输出的注意力控制降低和/或刺激-反应关联的破坏），这可能与帕金森病中的类似事件有关。
The present study examined the ability of rats subjected to bilateral 6-hydroxydopamine lesions of the terminal area of the nigrostriatal dopamine system to perform a prelearned reaction time task. This lesion model, the induction of a partial dopamine denervation of the striatum (74% depletion of dopamine striatal tissue content) with a retrograde degeneration of dopamine cell bodies in the substantia nigra, sparing the mesolimbic dopaminergic pathway, closely approximates the neuronal degeneration observed in human idiopathic Parkinson's disease. Rats were trained previously to release a lever, within a reaction time limit, after the presentation of a visual cue through reinforcement with food pellets, The onset of the light stimulus varied randomly after an unpredictable delay period of 0.25-1.0 s, Rats with dopaminergic lesions showed moderate to extensive performance deficits which were not compensated for the five postoperative weeks. More than half of the lesioned animals (64%) showed severe deficits, characterized by a concomitant increase in the number of anticipated (premature release of the lever before the visual cue) and delayed responses (lever release after the reaction time limit) with shortened reaction times in some cases, A smaller proportion (36%) of lesioned animals exhibited mild impairment of performance with a large increase in delayed responses and lengthening of reaction times but with no change in the number of anticipated responses. Asymmetric lesions had no effect on the reaction time performance. Examination of tyrosine hydroxylase immunostaining revealed that in the most impaired animals dopamine depletion was extensive in the medial striatum, whereas it was restricted to the dorsolateral striatum in the least impaired animals. Results suggest that a decrease in dopamine function at striatal level severely disrupts performance of a conditioned reaction time task. A partial dopamine depletion in the dorsolateral striatum induces motor initiation deficits (i.e. increases delayed response only), Larger striatal dopamine depletion may produce both motor and cognitive deficits (decrease in attentional control over response output and/or disruption of stimulus-response associations) that could be related to similar events in Parkinson's disease.