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人类失忆症和痴呆症的动物模型:大鼠海马体和杏仁核切除与5-羟色胺能及胆碱能阻断的比较

Animal models of human amnesia and dementia: hippocampal and amygdala ablation compared with serotonergic and cholinergic blockade in the rat.

作者信息

Dickson C T, Vanderwolf C H

机构信息

Department of Psychology, University of Western Ontario, London, Canada.

出版信息

Behav Brain Res. 1990 Dec 21;41(3):215-27. doi: 10.1016/0166-4328(90)90109-r.

DOI:10.1016/0166-4328(90)90109-r
PMID:2288673
Abstract

The behavioral effects of combined bilateral hippocampal and amygdala ablation (previously proposed as a model of human global amnesia) were compared to those seen with central blockade of the ascending cholinergic and serotonergic projections (a possible model of human global dementia) in male hooded rats. Rats were prepared with: (a) bilateral surgical lesions of the hippocampus and amygdala; (b) pharmacological blockade of central cholinergic and serotonergic function by systemic injections of scopolamine and p-chlorophenylalanine; and (c) neurotoxic lesions of the rostrally projecting serotonergic nuclei in the brainstem using intracerebral injections of 5,7-dihydroxytryptamine, later combined with scopolamine. The behavioral tests used were: an open field test, a swim-to-platform test, and a Lashley III maze. In all 3 tests, rats with either the neurotoxin lesions plus scopolamine or p-chlorophenylalanine plus scopolamine treatment showed greater impairments in comparison with controls than did the combined lesion group. These results indicate that simultaneous blockade of central serotonergic and cholinergic transmission has a greater effect on some aspects of the organization of behavior than large surgical lesions of the hippocampus and amygdala.

摘要

将双侧海马体和杏仁核联合切除(先前被提议作为人类全面性失忆症的模型)的行为学效应,与雄性带帽大鼠中上行胆碱能和5-羟色胺能投射的中枢阻断(人类全面性痴呆的一种可能模型)的行为学效应进行了比较。对大鼠进行了如下处理:(a) 海马体和杏仁核的双侧手术损伤;(b) 通过全身注射东莨菪碱和对氯苯丙氨酸对中枢胆碱能和5-羟色胺能功能进行药理学阻断;以及 (c) 使用脑内注射5,7-二羟色胺对脑干中向前投射的5-羟色胺能核进行神经毒性损伤,随后联合使用东莨菪碱。所使用的行为学测试包括:旷场试验、游向平台试验和拉什利III型迷宫试验。在所有这三项测试中,与对照组相比,接受神经毒素损伤加东莨菪碱或对氯苯丙氨酸加东莨菪碱治疗的大鼠表现出的损伤比联合损伤组更大。这些结果表明,与海马体和杏仁核的大型手术损伤相比,同时阻断中枢5-羟色胺能和胆碱能传递对行为组织的某些方面具有更大的影响。

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