Herrera-Marschitz M, Ungerstedt U
Brain Res. 1984 Dec 10;323(2):269-78. doi: 10.1016/0006-8993(84)90297-x.
It was proposed that apomorphine and the ergot derivative pergolide induce rotation in 6-hydroxy-dopamine (6-OHDA)-denervated rats by different receptor mechanisms, since these dopamine agonists induce different patterns of rotational behaviour, have different dose-response curves and are differently inhibited by neuroleptics acting on D1 or D2 type receptors. The synaptic continuation of the striatonigral pathway was interrupted in unilaterally 6-OHDA-lesioned rats by adding a kainic acid lesion to the 6-OHDA-lesioned nigra. This lesion affected apomorphine and pergolide rotation differently. After an initial short peak of contralateral rotation, apomorphine induced ipsilateral rotation that increased with dose, although a final contralateral peak was always maintained. The only change in pergolide rotation was a shift of the dose-response curve to the right. In another group of animals, the continuation of the striatonigral pathway was lesioned by unilateral kainic acid injections without previous 6-OHDA-lesions of the dopamine system. In these animals apomorphine but not pergolide induced rotational behaviour. In contrast, both drugs induced rotation in animals where all striatal efferents were lesioned unilaterally by kainic acid injections into one striatum. The results suggest that the apomorphine rotation is mainly dependent upon striatonigral pathways while the pergolide rotation is dependent upon other striatal efferent pathways.
有人提出,阿扑吗啡和麦角衍生物培高利特通过不同的受体机制诱导6-羟基多巴胺(6-OHDA)去神经支配大鼠的旋转行为,因为这些多巴胺激动剂诱导不同的旋转行为模式,具有不同的剂量-反应曲线,并且受到作用于D1或D2型受体的抗精神病药物的不同抑制。在单侧6-OHDA损伤的大鼠中,通过在6-OHDA损伤的黑质中添加 kainic 酸损伤来中断纹状体黑质通路的突触延续。这种损伤对阿扑吗啡和培高利特诱导的旋转有不同的影响。在最初短暂的对侧旋转高峰后,阿扑吗啡诱导同侧旋转,且随剂量增加,尽管最终总是保持对侧高峰。培高利特诱导的旋转唯一的变化是剂量-反应曲线向右移动。在另一组动物中,通过单侧注射 kainic 酸损伤纹状体黑质通路的延续,而之前多巴胺系统未进行6-OHDA损伤。在这些动物中,阿扑吗啡而非培高利特诱导旋转行为。相反,在通过向一侧纹状体注射 kainic 酸单侧损伤所有纹状体传出纤维的动物中,两种药物都诱导旋转。结果表明,阿扑吗啡诱导的旋转主要依赖于纹状体黑质通路,而培高利特诱导的旋转依赖于其他纹状体传出通路。