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单侧新纹状体损伤大鼠的纹状体移植——III. 从多巴胺依赖性运动不对称及熟练爪抓取缺陷中恢复

Striatal grafts in rats with unilateral neostriatal lesions--III. Recovery from dopamine-dependent motor asymmetry and deficits in skilled paw reaching.

作者信息

Dunnett S B, Isacson O, Sirinathsinghji D J, Clarke D J, Björklund A

机构信息

Department of Experimental Psychology, University of Cambridge, U.K.

出版信息

Neuroscience. 1988 Mar;24(3):813-20. doi: 10.1016/0306-4522(88)90069-3.

Abstract

This study investigated the functional capacity of intrastriatal grafts of embryonic striatal tissue in rats with unilateral ibotenic acid lesions of the neostriatum. The group of grafted rats was compared with lesion-alone and control groups for motor bias, as assessed by tests of rotation induced by dopaminergic, cholinergic and GABAergic drugs, and of skilled paw reaching. Unilateral striatal lesions induced marked ipsilateral turning to apomorphine and methamphetamine, which was substantially ameliorated in the grafted rats. Atropine induced similar rates of moderate (but non-significant) ipsilateral turning in the lesion and graft groups, whereas muscimol and gamma-acetylenic GABA induced no turning bias in any group. The lesioned rats showed a strong bias in their preference to use the paw ipsilateral to the lesion when reaching for food pellets, and a decline in reaching success with both paws. The grafts did not influence the ipsilateral paw preference in this task, but did provide a substantial improvement in the animal's reaching accuracy and ability to retrieve food with either paw. The results indicate that striatal grafts can provide a substantial amelioration of motor impairments induced by striatal lesions. Moreover they suggest that the graft's influence on the host brain is itself under the functional regulation of an afferent dopaminergic input from the host brain.

摘要

本研究调查了胚胎纹状体组织脑内移植对单侧新纹状体鹅膏蕈氨酸损伤大鼠的功能恢复情况。通过多巴胺能、胆碱能和GABA能药物诱导的旋转试验以及熟练的爪抓取试验评估运动偏向,将移植组大鼠与单纯损伤组和对照组进行比较。单侧纹状体损伤导致大鼠对阿扑吗啡和甲基苯丙胺产生明显的同侧旋转,而移植组大鼠的这种旋转行为得到了显著改善。阿托品在损伤组和移植组中诱导相似的中等程度(但无统计学意义)同侧旋转率,而蝇蕈醇和γ-乙炔基甘氨酸在任何组中均未诱导旋转偏向。损伤大鼠在抓取食物颗粒时强烈倾向于使用损伤同侧的爪子,并且双爪抓取成功率下降。移植在该任务中并未影响同侧爪偏好,但确实显著提高了动物的抓取准确性以及用任一爪子获取食物的能力。结果表明,纹状体移植可显著改善纹状体损伤所致的运动障碍。此外,研究结果提示移植对宿主脑的影响本身受宿主脑传入多巴胺能输入的功能调节。

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