Hadadianpour Zahra, Fatehi Farangis, Ayoobi Fateme, Kaeidi Ayat, Shamsizadeh Ali, Fatemi Iman
a Physiology-Pharmacology Research Center , Rafsanjan University of Medical Sciences , Rafsanjan , Iran.
b Department of Physiology and Pharmacology, School of Medicine , Rafsanjan University of Medical Sciences , Rafsanjan , Iran.
Neurol Res. 2017 Sep;39(9):845-851. doi: 10.1080/01616412.2017.1352185. Epub 2017 Jul 12.
The aim of this study was to evaluate the effect of orexin-A (OX-A) and the orexin-1 receptor antagonist SB-334867 (SB) on motor and cognitive functions in a rat model of Parkinson's disease.
Parkinson was induced by intracerebroventricular (i.c.v) injection of 6- hydroxydopamine (6-OHDA) (200 μg/rat). 72 h later, the treatment was initiated by i.c.v administration of SB (30 nmol/rat) and/or OX-A (0.3 nmol/rat) for 10 days. Motor functions were monitored using rotarod and hanging tests. Cognitive function was assessed by passive avoidance test (Shuttle box). Results: OX-A administration in 6-OHDA treated rats remarkably increased the time which animals run on rod (in rotarod test) and also the latency to fall (in hanging test) (P < 0.01 and P < 0.001, respectively). Conversely, administration of SB in 6-OHDA-treated rats decreased the mentioned indices (P < 0.05 for latency to fall). Administration of agonist and/or antagonist of orexin-1 receptors had no significant effect on 6-OHDA induced cognitive impairment in rats.
Results of this study suggest that the orexinergic system might be involved in sensory-motor deficits of Parkinson's disease.
本研究旨在评估食欲素-A（OX-A）和食欲素-1受体拮抗剂SB-334867（SB）对帕金森病大鼠模型运动和认知功能的影响。
通过脑室内（i.c.v）注射6-羟基多巴胺（6-OHDA）（200μg/只大鼠）诱导帕金森病模型。72小时后，通过脑室内给予SB（30nmol/只大鼠）和/或OX-A（0.3nmol/只大鼠）进行为期10天的治疗。使用转棒试验和悬垂试验监测运动功能。通过被动回避试验（穿梭箱）评估认知功能。结果：在6-OHDA处理的大鼠中给予OX-A显著增加了动物在转棒上奔跑的时间（转棒试验）以及掉落潜伏期（悬垂试验）（分别为P<0.01和P<0.001）。相反，在6-OHDA处理的大鼠中给予SB降低了上述指标（掉落潜伏期P<0.05）。给予食欲素-1受体激动剂和/或拮抗剂对6-OHDA诱导的大鼠认知障碍无显著影响。
本研究结果表明，食欲素能系统可能参与帕金森病的感觉运动缺陷。
