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Lesion of subthalamic nucleus in Parkinsonian rats : effects of dopamine D1 and D2 receptor agonists on the neuronal activities of the substantia nigra pars reticulata

Other Titles
 도파민 수용체 효능제와 시상밑 
 Dept. of Neurosurgery (신경외과학교실) 
Issue Date
Dept. of Medicine/박사
[한글]파킨슨병 모델의 흰쥐에 대하여 시상밑핵에 병변을 만들고 도파민 수용체 효능제를 함께 투여하여, 상승 효과를 기대할 수 있으리라는 가정하에 흑질 망상대에서 발화율과 발화 양상을 측정하였다. 몸무게 200-250 g의 수컷 흰쥐 (Sprague-Dawley rat)를 이용하였고 6-hydroxydopamine을 뇌정위 기구를 이용하여 내측전뇌다발에 주입하여 파킨슨병 모델을 제작하였다. 시상밑핵에는 kainic acid를 뇌정위 기구를 이용하여 주입하여 치료 모델을 제작하였으며, 도파민 제1 수용체 효능제인 SKF38393과 도파민 제 2 수용체 효능제인 Quinpirole은 선조체에 주입한 후 흑질 망상대에서 단일 세포의 발화유과 발화 양상을 측정하여 비교하였다. 정상군에 비하여 파킨슨병 모델에서 발화율과 극파의 비율이 증가하였고, 시상밑핵 병변을 만든 후에 의미 있게 발화율의 감소, 극파의 비율이 감소하였다. SKF38393과 Quinpirole을 주입하였을 때 파킨슨병 모델에서는 발화율과 극파 비율의 감소를 확인 할 수 있었으며, 시상밑핵 병변에 더하여 Quinpirole을 주입하였을 경우에는 발화율이 증가하였고 극파의 비율이 증가하였다.
[영문]Object. It was hypothesized that dopamine agonist administration and subthalamic nucleus (STN) lesion in the rat might have a synergistic effect on the neuronal activities of substantia nigra pars reticulata (SNpr) as observed in patients with Parkinson’s disease. The effects of SKF38393 (a D1 receptor agonist) and Quinpirole (a D2 receptor agonist) were compared in parkinsonian rat models with 6- hydroxydopamine (6-OHDA) after STN lesion. The changes of the firing rates and firing patterns of SNpr neurons were analyzed.Methods. SKF38393 and Quinpirole were consecutively injected intrastriatally. SNpr was microrecorded to ascertain the activity of the basal ganglia output structure. The effect of SKF38393 or Quinpirole injection on the firing rate and firing patterns of SNpr was investigated in medial forebrain bundle (MFB) lesioned rats and in MFB + STN lesioned rats.Results. The administration of SKF38393 decreased SNpr neuronal firing rates in the lesioned rats, but did not alter the mean neuronal firing rate in the SNpr neurons of MFB+ STN lesioned rats, nor induce significant changes in the percentage of burst neurons. In rats prepared from 6-OHDA, Quinpirole significantly decreased the spontaneous firing rate. However, after an additional STN lesion, it induced a significant change in the percentage of burst neurons.Conclusions. The results demonstrated that STN lesion decreases SNpr hyperactivity and the proportion of burst neurons among total neurons, but that dopamine receptor agonists, such as SKF38393 and Quinpirole, did not change the firing pattern.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 3. Dissertation
Yonsei Authors
Park, Yong Sook(박용숙)
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