Motor regulation system in a Parkinson's disease animal model

大剂量左旋多巴可降低黑质多巴胺能神经元的放电频率。这种现象可能是由于黑质内通过自身感受器的负反馈机制。长期服用左旋多巴是否影响SNC DA仍不清楚。我们评估SNC DA功能使用放电率和多巴胺能末梢兴奋性的多巴胺神经元在雄性SD大鼠。两组动物;第一组（n=19）每天腹腔注射左旋多巴（100 mg/kg）和卡比多巴（25 mg/kg），连续60天;第二组（n=27）为对照组。用微量移液器获得SNC DA的细胞外单个单位记录。多巴胺能末梢兴奋性被确定为由新纹状体电刺激诱发的逆行反应的阈值。与对照组相比，左旋多巴组的放电频率无显著性差异，但终末兴奋性降低。终末兴奋性降低可能与抑制纹状体多巴胺释放有关。这一发现似乎与长期治疗后左旋多巴治疗反应减弱的临床观察有关。

In large doses, levodopa decreases the firing rate of rat dopaminergic neurons in the substantia nigrapars compacta (SNC DA). This phenomenon may be due to a negative feedback mechanism through autoreceptors within the substantia nigra. Whether chronic levodopa administration influences on SNC DA remain unclear. We evaluated SNC DA function using the firing rate and dopaminergic terminal excitability of dopamine neurons in male Sprague-Dawley rats. Two groups of animals ; the first group (n=19 rats) received daily intraperitoneal injection of levodopa (100mg/kg) and carbidopa (25mg/kg) for 60 days, while the second group (n=27) was the control. Extracellular single unit recordings of SNC DA were obtained with micropipettes. Dopaminergic terminal excitability was determined as the threshold of antidromic responses evoked by neostriatal electrostimulation. There were no significant differences in the firing rate between two groups, but the levodopa group showed a decrease in the terminal excitability compared with that in the control group. The decrease of terminal excitability may be related to impare striatal dopamine release. This finding appears to be related the clinical observation that L-dopa therapeutic response diminishes following chronic treatment.