Thomas J, Wang J, Takubo H, Sheng J, de Jesus S, Bankiewicz K S
CNS Implantation & Regeneration Unit, NINDS, National Institutes of Health, Bethesda, Maryland 20892.
Exp Neurol. 1994 Apr;126(2):159-67. doi: 10.1006/exnr.1994.1054.
The main focus of the present study was to define the rotational response of 6-hydroxydopamine-lesioned rats to dopaminergic agonists to separate the partially lesioned rats from those having complete substantia nigra (SN) and ventral tegmental area (VTA) lesions. Animals were challenged by amphetamine and L-DOPA for 10 consecutive weeks. There was a correlation between rotational behavior and extent of midbrain cell loss. Rats with complete SN and < 40% VTA lesion turned more than 5 times/min after amphetamine administration, but not after L-DOPA; animals with complete SN and 40-80% VTA lesions turned vigorously following amphetamine and began turning after L-DOPA administration. Rats with complete SN and VTA lesions turned less after amphetamine than the other two groups, while their turning after L-DOPA administration increased. Extracellular dopamine (DA) measured by microdialysis, intracellular DA measured by postmortem tissue punches, and tyrosine hydroxylase-immunoreactive cell count in SN and VTA were also evaluated. It appears that the dopaminergic cells in the lateral VTA affect DA concentration in the medial caudate nucleus. In the nucleus accumbens of the lesioned side, DA release and metabolism substantially increased with the larger VTA lesion. Dopamine turnover rate in the caudate was also higher in the group with < 40% VTA lesion.
本研究的主要重点是确定6-羟基多巴胺损伤大鼠对多巴胺能激动剂的旋转反应，以区分部分损伤大鼠与黑质（SN）和腹侧被盖区（VTA）完全损伤的大鼠。连续10周用苯丙胺和左旋多巴对动物进行激发试验。旋转行为与中脑细胞损失程度之间存在相关性。SN完全损伤且VTA损伤小于40%的大鼠在给予苯丙胺后每分钟旋转超过5次，但给予左旋多巴后则不会；SN完全损伤且VTA损伤40%-80%的动物在给予苯丙胺后剧烈旋转，并在给予左旋多巴后开始旋转。SN和VTA完全损伤的大鼠在给予苯丙胺后的旋转次数少于其他两组，而它们在给予左旋多巴后的旋转次数增加。还评估了通过微透析测量的细胞外多巴胺（DA）、通过死后组织打孔测量的细胞内DA以及SN和VTA中酪氨酸羟化酶免疫反应性细胞计数。似乎外侧VTA中的多巴胺能细胞会影响内侧尾状核中的DA浓度。在损伤侧的伏隔核中，随着VTA损伤面积增大，DA释放和代谢显著增加。VTA损伤小于40%的组中尾状核的多巴胺周转率也更高。
