Gui Zhen-Hua, Liu Jian, Wang Yong, Ali Umar, Wang Tao, Chen Li
Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, People's Republic of China.
Chin J Physiol. 2011 Apr 30;54(2):96-104. doi: 10.4077/cjp.2011.amm014.
Previous studies have suggested that R-apomorphine (R-APO), a non-selective dopamine (DA) receptor agonist, has neuroprotective effects in the experimental models of Parkinson's disease (PD). In this study, we investigated the effects of chronic, systemic treatment with R-APO in the firing activity of substantia nigra pars compacta (SNc) DA neurons in 6-hydroxydopamine (6-OHDA) partially lesioned rats. In the 6-OHDA-lesioned rats treated with vehicle, injection of 6-OHDA (20.1 microg) into the striatum produced a partial lesion causing 41% loss of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the SNc. In the partially lesioned rats, chronic, systemic treatment of R-APO (10 mg/kg/day, s.c., 11 days) attenuated loss of TH-ir neurons in the SNc. The partial lesion of the nigrostriatal pathway and R-APO treatment did not change the firing rate and firing pattern of DA neurons in the SNc of rats. In contrast, the R-APO treatment increased the number of spontaneously active DA neurons of the SNc in the partially lesioned rats, while the lesion decreased the number of spontaneously active DA neurons. In addition, the chronic R-APO treatment decreased the responsiveness of the DA neurons to intravenously administrated R-APO in the partially lesioned rats. These results indicate that chronic, systemic R-APO treatment has the neuroprotective effect, and reverses the decrease in the number of spontaneously active DA neurons in the SNc whereas the treatment induces a reduction in the sensitivity of DA receptors in the SNc to R-APO stimulation in this model.
先前的研究表明，R-阿扑吗啡（R-APO）作为一种非选择性多巴胺（DA）受体激动剂，在帕金森病（PD）实验模型中具有神经保护作用。在本研究中，我们调查了对6-羟基多巴胺（6-OHDA）部分损伤大鼠的黑质致密部（SNc）DA神经元放电活动进行慢性全身给予R-APO的效果。在用赋形剂处理的6-OHDA损伤大鼠中，向纹状体注射6-OHDA（20.1微克）产生了部分损伤，导致SNc中酪氨酸羟化酶免疫反应性（TH-ir）神经元损失41%。在部分损伤大鼠中，慢性全身给予R-APO（10毫克/千克/天，皮下注射，11天）可减轻SNc中TH-ir神经元的损失。黑质纹状体通路的部分损伤和R-APO处理并未改变大鼠SNc中DA神经元的放电频率和放电模式。相反，R-APO处理增加了部分损伤大鼠SNc中自发活动的DA神经元数量，而损伤则减少了自发活动的DA神经元数量。此外，慢性R-APO处理降低了部分损伤大鼠中DA神经元对静脉注射R-APO的反应性。这些结果表明，慢性全身给予R-APO具有神经保护作用，并逆转了SNc中自发活动的DA神经元数量的减少，而在该模型中，这种处理导致SNc中DA受体对R-APO刺激的敏感性降低。
