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血管紧张素IV类似物减轻东莨菪碱诱导的空间学习障碍

Attenuation of scopolamine-induced spatial learning impairments by an angiotensin IV analog.

作者信息

Pederson E S, Harding J W, Wright J W

机构信息

Program in Neuroscience, Washington State University, Pullman 99164, USA.

出版信息

Regul Pept. 1998 Jun 30;74(2-3):97-103. doi: 10.1016/s0167-0115(98)00028-7.

DOI:10.1016/s0167-0115(98)00028-7
PMID:9712169
Abstract

Recently, a receptor for the angiotensin II(3-8) (Ang IV) hexapeptide, was discovered in the hippocampus, suggesting a possible role in learning. The present study utilized intracerebroventricularly (icv) infused scopolamine hydrobromide (scop) to disrupt spatial learning in the circular water maze, followed by the Ang IV analog norleucine1-Ang IV (Nle1-Ang IV), to restore normal performance. Rats were icv pretreated with either scop or artificial cerebrospinal fluid (aCSF) followed by either icv injected Nle1-Ang IV or aCSF, and then behaviourally tested. During acquisition training, each animal's latency to locate the platform, path distance, speed, and efficiency ratios were measured. A probe trial was conducted on the final day of training and the time spent in the target quadrant and the number of crossings over the former location of the platform (annulus crossings) were observed. The results indicate that those animals treated with scop followed by aCSF performed poorly during acquisition training as compared with controls. In contrast, those animals that received scop followed by Nle1-Ang IV attained equivalent latencies, distances, and efficiency ratios to find the platform as those achieved by controls. There were no observed differences in swimming speed, thus arguing against drug-induced motor impairment. During the probe trial, animals treated with scop followed by aCSF spent less time in the target quadrant and made fewer annulus crossings as compared to controls, while the scop, Nle'-Ang IV treated animals performed equivalently to controls. These results suggest that Nle1-Ang IV acts to counteract the disruption of spatial learning induced by scopolamine.

摘要

最近,在海马体中发现了血管紧张素II(3 - 8)(Ang IV)六肽的一种受体,这表明其在学习过程中可能发挥作用。本研究通过脑室内(icv)注入氢溴酸东莨菪碱(scop)来干扰圆形水迷宫中的空间学习,随后使用Ang IV类似物正亮氨酸1 - Ang IV(Nle1 - Ang IV)来恢复正常表现。大鼠先经icv给予scop或人工脑脊液(aCSF)预处理,随后经icv注射Nle1 - Ang IV或aCSF,然后进行行为测试。在习得训练期间,测量每只动物找到平台的潜伏期、路径距离、速度和效率比。在训练的最后一天进行探针试验,观察在目标象限花费的时间以及越过平台先前位置的次数(环周穿越次数)。结果表明,与对照组相比,先给予scop后给予aCSF处理的动物在习得训练期间表现较差。相比之下,那些先接受scop后接受Nle1 - Ang IV处理的动物找到平台的潜伏期、距离和效率比与对照组相当。未观察到游泳速度有差异,因此排除了药物诱导的运动障碍。在探针试验期间,与对照组相比,先给予scop后给予aCSF处理的动物在目标象限花费的时间更少,环周穿越次数也更少,而接受scop、Nle1 - Ang IV处理的动物表现与对照组相当。这些结果表明,Nle1 - Ang IV可抵消东莨菪碱诱导的空间学习障碍。

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