Abrous D N, Rivet J M, Le Moal M, Herman J P
INSERM U-259-Université de Bordeaux II, France.
Brain Res. 1990 Sep 3;526(2):195-202. doi: 10.1016/0006-8993(90)91221-2.
The ascending dopaminergic system of adult or 3-day-old rats has been unilaterally lesioned by the intraparenchymal injection of 6-hydroxydopamine aimed at the medial forebrain bundle at the level of the lateral hypothalamus. Nigral dopaminergic neurons disappeared following the lesion on the lesioned side in both experimental groups while the depletion of the ventral tegmental area was less extensive, especially following the neonatal lesion. Striatal regions were markedly depleted of their dopaminergic innervation, although the magnitude of the depletion was slightly higher following the adult stage lesion as judged on the basis of biochemical measurements (99% vs. 96%). Amphetamine (5 mg/kg) evoked an identical ipsilateral rotational response in both experimental groups. Moreover, this rotational response was blocked both by the specific D1 receptor blocker SCH-23390 (0.1 mg/kg) and the specific D2 receptor antagonist raclopride (2 mg/kg). Likewise, contralateral rotational responses to the directly acting D1 and D2 dopamine receptor agonists SKF-38393 (2.5 mg/kg) and LY-171555 (0.15 mg/kg) were similar in both experimental groups, both qualitatively and quantitatively. These results confirm conclusions obtained in earlier works, and indicate that reported differences in behavioral deficits between animals lesioned as neonates or adults are not related to differing modifications of striatal DA receptor sensitivities.
通过向成年或3日龄大鼠外侧下丘脑水平的内侧前脑束实质内注射6-羟基多巴胺,对其多巴胺能上行系统进行单侧损伤。在两个实验组中,损伤侧黑质多巴胺能神经元在损伤后消失,而腹侧被盖区的多巴胺能神经元耗竭程度较轻,尤其是在新生期损伤后。纹状体区域的多巴胺能神经支配明显减少,尽管根据生化测量判断,成年期损伤后多巴胺能神经支配的减少幅度略高(99%对96%)。苯丙胺(5mg/kg)在两个实验组中引起相同的同侧旋转反应。此外,这种旋转反应被特异性D1受体阻滞剂SCH-23390(0.1mg/kg)和特异性D2受体拮抗剂雷氯必利(2mg/kg)阻断。同样,两个实验组对直接作用的D1和D2多巴胺受体激动剂SKF-38393(2.5mg/kg)和LY-171555(0.15mg/kg)的对侧旋转反应在质量和数量上相似。这些结果证实了早期研究得出的结论,并表明报道的新生期或成年期损伤动物行为缺陷的差异与纹状体多巴胺受体敏感性的不同改变无关。