Barnéoud P, Parmentier S, Mazadier M, Miquet J M, Boireau A, Dubédat P, Blanchard J C
Rhône-Poulenc Rorer S.A., Département de Biologie, Vitry-sur-Seine, France.
Neuroscience. 1995 Aug;67(4):837-48. doi: 10.1016/0306-4522(95)00112-v.
This study compares certain behavioural consequences of partial and complete unilateral lesions of the dopaminergic mesotelencephalic system. We investigated skilled forelimb use, rotations induced by apomorphine and amphetamine, and dopaminergic metabolism of the nigrostriatal system of rats that had received a unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. The rats classified Apo(+), that rotated after the administration of apomorphine, had a complete lesion of the nigrostriatal system, whereas those classified Apo(-), that did not rotate after the administration of apomorphine, had a partial lesion of the nigrostriatal system. In the Apo(+) rats, 99.8% of the dopamine in the striatum was depleted, as was 85% of that in the substantia nigra. For the Apo(-) rats, 72% of the dopamine in the striatum was depleted as was 56% of that in the substantia nigra. When investigated with the staircase test, the animals with the most severe dopamine depletions were those most impaired in the paw reaching task. Complete and partial unilateral depletions of the dopaminergic mesotelencephalic system impaired the hierarchic phases of paw reaching differently. A complete dopamine depletion, but not a partial one, decreased the number of attempts made with the contralateral paw, and induced a bias towards the ipsilateral paw. A partial dopamine lesion impaired the sensorimotor co-ordination of both paws, whereas the complete dopamine lesion had a greater effect on the contralateral paw than on the ipsilateral paw. The mild paw reaching impairments observed in animals with moderate depletions of dopamine are proposed as a model of the early symptoms of Parkinson's disease that may be useful for the development of protective or restorative therapies.
本研究比较了多巴胺能中脑边缘系统部分和完全单侧损伤的某些行为后果。我们研究了接受内侧前脑束单侧注射6-羟基多巴胺的大鼠的熟练前肢使用情况、阿扑吗啡和苯丙胺诱导的旋转以及黑质纹状体系统的多巴胺能代谢。分类为阿扑吗啡（+）的大鼠，即注射阿扑吗啡后旋转的大鼠，黑质纹状体系统有完全损伤，而分类为阿扑吗啡（-）的大鼠，即注射阿扑吗啡后不旋转的大鼠，黑质纹状体系统有部分损伤。在阿扑吗啡（+）大鼠中，纹状体中99.8%的多巴胺被耗尽，黑质中85%的多巴胺也被耗尽。对于阿扑吗啡（-）大鼠，纹状体中72%的多巴胺被耗尽，黑质中56%的多巴胺被耗尽。当用阶梯试验进行研究时，多巴胺耗尽最严重的动物在爪子够取任务中受损最严重。多巴胺能中脑边缘系统的完全和部分单侧耗尽对爪子够取的不同层次阶段有不同程度的损害。完全多巴胺耗尽而非部分耗尽会减少对侧爪子的尝试次数，并导致偏向同侧爪子。部分多巴胺损伤会损害双爪的感觉运动协调，而完全多巴胺损伤对侧爪的影响比对同侧爪的影响更大。多巴胺中度耗尽的动物中观察到的轻微爪子够取损伤被认为是帕金森病早期症状的模型，这可能有助于保护性或恢复性疗法的开发。
