Motor regulation system in a Parkinson's disease animal model

帕金森病动物模型中的运动调节系统

• 批准号: 06670655
• 负责人: TAKEUCHI Hiroaki
• 金额: $ 1.02万
• 依托单位: Kagawa medical school
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670655/
• 关键词: dopaminergic neurons; substantia nigra pars compacta; levodopa; terminal excitability; 黒質線条件ドーパミンニューロン; L-Dopa

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.

大剂量左旋多巴可降低黑质致密带多巴胺能神经元的放电频率。这种现象可能是由于黑质内自身受体的负反馈机制所致。长期服用左旋多巴是否对SNC DA的影响尚不清楚。我们用雄性SD大鼠的多巴胺能神经元的放电频率和多巴胺能终末兴奋性来评价黑质多巴胺的功能。两组动物，第一组大鼠(n=19)每日腹腔注射左旋多巴(100 mg/kg)和卡比多巴(25 mg/kg)，连续60天，第二组(n=27)为对照组。用微吸管记录细胞外单个单位的SNCDA。多巴胺能终末兴奋性被确定为新纹状体电刺激诱发逆行反应的阈值。两组的放电频率无显著差异，但左旋多巴组的终末兴奋性较对照组降低。终末兴奋性降低可能与纹状体多巴胺释放减少有关。这一发现似乎与慢性治疗后L-多巴治疗反应减弱的临床观察有关。