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通过向基底核区域注射秋水仙碱所产生的放射状臂迷宫缺陷,可被胆碱能药物改善。

Radial-arm maze deficits produced by colchicine administered into the area of the nucleus basalis are ameliorated by cholinergic agents.

作者信息

Tilson H A, McLamb R L, Shaw S, Rogers B C, Pediaditakis P, Cook L

机构信息

Laboratory of Behavioral and Neurological Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.

出版信息

Brain Res. 1988 Jan 12;438(1-2):83-94. doi: 10.1016/0006-8993(88)91326-1.

Abstract

Rats were given bilateral injections of colchicine into the area of the nucleus basalis. Colchicine produced dose-dependent alterations in the acquisition of a food-reinforced working-memory task. Colchicine-induced deficits in maze performance were attenuated by cholinergic agents, including physostigmine, RS-86 (2-ethyl-8-methyl-2,8-diazospiro-(4,5)-decan-1,3-dione-hydro bromide) and nicotine. Naloxone and vasopressin did not affect radial-arm maze performance of colchicine-treated rats. Subsequent neurochemical analysis showed that colchicine decreased choline acetyltransferase (ChAT) activity and levels of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in the neocortex. However, ChAT activity and other neurochemical measures were not altered in the hippocampus or corpus striatum. Histological assessment indicated damage limited to the injection in the area of the nucleus basalis and enlarged cerebrolateral ventricles. These data suggest the possible utility of the colchicine model in the study of cognitive deficits associated with neurodegenerative diseases.

摘要

给大鼠双侧注射秋水仙碱至基底核区域。秋水仙碱在食物强化工作记忆任务的习得过程中产生剂量依赖性改变。秋水仙碱诱导的迷宫表现缺陷可被胆碱能药物减弱,包括毒扁豆碱、RS - 86(2 - 乙基 - 8 - 甲基 - 2,8 - 二氮杂螺-(4,5)-癸烷 - 1,3 - 二酮氢溴酸盐)和尼古丁。纳洛酮和加压素不影响经秋水仙碱处理的大鼠的放射状臂迷宫表现。随后的神经化学分析表明,秋水仙碱降低了新皮层中胆碱乙酰转移酶(ChAT)的活性以及去甲肾上腺素、多巴胺、3,4 - 二羟基苯乙酸、血清素和5 - 羟基吲哚乙酸的水平。然而,海马体或纹状体中的ChAT活性及其他神经化学指标未发生改变。组织学评估表明损伤仅限于基底核区域的注射部位及大脑侧脑室扩大。这些数据表明秋水仙碱模型在研究与神经退行性疾病相关的认知缺陷方面可能具有实用性。

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