多巴胺D1受体激动剂对异动症大鼠电生理活动的影响

Functional Changes of D1 Dopamine Receptor in Striatal Neurons of Rats with Levodopa-induced Dyskinesias

目的:探讨多巴胺D1受体在异动症(LID)发生机制中的作用。方法:复制成功的帕金森病(PD)大鼠35只,分为PD组13只,另22只应用复方左旋多巴治疗28d诱发LID大鼠模型,取12只为LID组。第29天取10只在复方左旋多巴治疗前15min腹腔注射MK-801(MK-801组)。采用微电极细胞外记录技术检测LID组大鼠纹状体棘状神经元(SMSNs)电生理活动。尾静脉注射多巴胺D1受体激动剂(SKF-38393)、拮抗剂(SCH-12280)观察神经元电生理活动变化。结果:LID组SMSNs的自发性电活动较对照组(10只正常大组)及MK-801组、PD组明显增多(P<0.01和0.05),而对照组与MK-800组比较则差异无显著性意义。SKF-38393对LID组大鼠SMSNs自发性电活动的抑制作用呈浓度依赖性,LID组与对照组、MK-801组和PD组比较明显下降(P<0.01和0.05),PD组与MK801组比较差异无显著性意义。结论:LID大鼠SMSNs的自发性电活动增强,D1受体敏感性增高;通过SKF-38393可以阻抑或减轻LID的发生。

Objective： To clarify the functional changes of D1 Dopamine receptor on striatal medium-spiny neurons （SMSNs） of rats with levedopa-induced dyskinesias （LID）. Methods： PD rats were treated with chronic intermittent Ldopa celiac injection for 28 days to get the LID rats. On the day 29, the animals were given an acute administration of MK-801 15 min before levodopa treatment. Electrophysiological characteristics were studied by extracellular recording in all rats. D1 dopamine agonists （SKF-38393） were injected from tail vein. The discharge changes caused by D1 Dopamine agonists were observed. Results： Spontaneous firing rates in striatum of LID group were significantly more than those in control （P〈0.01）, PD （P〈0.05） and MK-801 groups （P〈0.01）, respectively. In LID group, the inhibitory responses of SMSNs to administration of SKF-38393 were significantly increased and 50 % inhibiting concentration （ICS00） for SKF-38393 was significantly reduced in LID group as compared to controls （P〈0. 01）, PD （P〈0.05） and MK-801 treatment groups （P〈0.01）. Spontaneous firing rates and ICS0s for SKF-38393 of SMSNs had no marked difference between control and MK-801 treatment groups （P〉0.05）. Conclusion： The sensitivity of D1 receptor was enhanced in LID rats and it may cause the change of spontaneous electrophysiological characteristics. So occurrence of LID may be blocked or decreased by inhibition of D1 receptor.