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通过脑室内注射3-甲基胆碱抑制胆碱转运的一些行为学效应。

Some behavioral effects of suppressing choline transport by cerebroventricular injection of hemicholinium-3.

作者信息

Russell R W, Macri J

出版信息

Pharmacol Biochem Behav. 1978 Apr;8(4):399-403. doi: 10.1016/0091-3057(78)90076-x.

DOI:10.1016/0091-3057(78)90076-x
PMID:674251
Abstract

Evidence supports the proposition that the high affinity Ch uptake system associated with cholinergic nerve terminals can be the rate limiting step in the synthesis of the neurotransmitter, acetylcholine. The present experiment was designed to test the hypothesis that variations of the system would be reflected selectively in changes of conditioned avoidance behavior. HC-3, which primarily affects the high affinity component of Ch transport thus reducing endogenous levels of ACh and the synthetic capacity of cholinergic nerve terminals, was administered cerebroventricularly at 5 doses ranging from 0.0 (saline control) to 10.0 microgram. Whole brain ACh levels determined by GCMS analysis following microwave fixation ranged from 25.0 to 5.0 nmol/g-1. Trend analyses demonstrate a precise dose dependent relation between neurochemical and behavioral variables: median trials to condition increased as ACh level decreased. More detailed analyses of the results lead to the interpretation that suppression of high affinity Ch transport in brain is associated with deficiencies in the use of information and not with sensory input and storage nor with motor output.

摘要

有证据支持这样的观点,即与胆碱能神经末梢相关的高亲和力胆碱摄取系统可能是神经递质乙酰胆碱合成中的限速步骤。本实验旨在检验以下假设:该系统的变化会选择性地反映在条件性回避行为的改变中。HC - 3主要影响胆碱转运的高亲和力成分,从而降低乙酰胆碱的内源性水平和胆碱能神经末梢的合成能力,通过脑室内注射给予5种剂量,范围从0.0(生理盐水对照)到10.0微克。在微波固定后通过气相色谱 - 质谱分析测定的全脑乙酰胆碱水平在25.0至5.0 nmol/g - 1之间。趋势分析表明神经化学和行为变量之间存在精确的剂量依赖关系:随着乙酰胆碱水平降低,条件化的中位试验次数增加。对结果进行更详细的分析得出的解释是,脑中高亲和力胆碱转运的抑制与信息利用不足有关,而与感觉输入和存储以及运动输出无关。

相似文献

1
Some behavioral effects of suppressing choline transport by cerebroventricular injection of hemicholinium-3.通过脑室内注射3-甲基胆碱抑制胆碱转运的一些行为学效应。
Pharmacol Biochem Behav. 1978 Apr;8(4):399-403. doi: 10.1016/0091-3057(78)90076-x.
2
Studies on the behavioral and biochemical effects of hemicholinium in vivo.体内毒蕈碱对行为和生化影响的研究。 (注:这里原文中的hemicholinium有误,正确的应该是hemicholinium-3,中文名称是毒蕈碱,根据纠正后的内容进行的翻译)
J Pharmacol Exp Ther. 1979 Jul;210(1):91-7.
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Regulation of acetylcholine synthesis in the presence of hemicholinium mustard.
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The effect of hemicholinium-3 on choline and acetylcholine levels in a sympathetic ganglion.毒扁豆碱-3对交感神经节中胆碱和乙酰胆碱水平的影响。
Can J Physiol Pharmacol. 1975 Jun;53(3):451-7. doi: 10.1139/y75-064.
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Inhibition of high affinity choline transport attenuates both cholinergic and non-cholinergic effects of ethylcholine aziridinium (AF64A).抑制高亲和力胆碱转运可减弱氮丙啶乙基胆碱(AF64A)的胆碱能和非胆碱能效应。
Brain Res. 1989 May 22;487(2):238-44. doi: 10.1016/0006-8993(89)90828-7.
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Identification of sodium-dependent, high-affinity choline uptake sites in rat brain with [3H]hemicholinium-3.用[3H]半胱氨酸-3鉴定大鼠脑中钠依赖性高亲和力胆碱摄取位点。
J Neurochem. 1986 Feb;46(2):483-8. doi: 10.1111/j.1471-4159.1986.tb12993.x.
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Hemicholinium-3-resistant choline uptake system linked to acetylcholine synthesis in the rat hippocampus.与大鼠海马体中乙酰胆碱合成相关的对毒扁豆碱-3有抗性的胆碱摄取系统。
Neurosci Lett. 1989 Oct 23;105(1-2):211-4. doi: 10.1016/0304-3940(89)90039-6.
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The effect of hemicholinium on behavior and on brain acetylcholine and choline in the rat.毒扁豆碱对大鼠行为以及脑内乙酰胆碱和胆碱的影响。
Psychopharmacol Commun. 1975;1(1):15-27.
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Amnesia produced by intracerebroventricular injections of hemicholinium-3 in mice was prevented by pretreatment with piracetam-like compounds.
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Effect of oxiracetam and piracetam on central cholinergic mechanisms and active-avoidance acquisition.奥拉西坦和吡拉西坦对中枢胆碱能机制及主动回避学习的影响。
Clin Neuropharmacol. 1986;9 Suppl 3:S39-47.

引用本文的文献

1
Effects of lithium on behavioral reactivity: relation to increases in brain cholinergic activity.
Psychopharmacology (Berl). 1981;73(2):120-5. doi: 10.1007/BF00429201.
2
Cholinergic learning deficits in the marmoset produced by scopolamine and ICV hemicholinium.
Psychopharmacology (Berl). 1984;83(4):340-5. doi: 10.1007/BF00428542.
3
Molecular composition of the phosphatidylcholines produced by the phospholipid methylation pathway in rat brain in vivo.大鼠脑内磷脂甲基化途径产生的磷脂酰胆碱的分子组成(体内研究)
Biochem J. 1987 Jun 1;244(2):325-30. doi: 10.1042/bj2440325.
4
Behavioral and physiological effects of an aziridinium analog of oxotremorine (BM130).
Psychopharmacology (Berl). 1986;88(1):24-32. doi: 10.1007/BF00310508.
5
Hemicholinium-3 impairs spatial learning and the deficit is reversed by cholinomimetics.半胱氨酸-3会损害空间学习能力,而拟胆碱药可逆转这种缺陷。
Psychopharmacology (Berl). 1989;98(3):347-56. doi: 10.1007/BF00451686.
6
Therapeutic effect of THA on hemicholinium-3-induced learning impairment is independent of serotonergic and noradrenergic systems.全髋关节置换术对毒蕈碱3诱导的学习障碍的治疗效果独立于5-羟色胺能和去甲肾上腺素能系统。
Psychopharmacology (Berl). 1990;101(3):376-83. doi: 10.1007/BF02244057.
7
Attentional functions of the forebrain cholinergic systems: effects of intraventricular hemicholinium, physostigmine, basal forebrain lesions and intracortical grafts on a multiple-choice serial reaction time task.前脑胆碱能系统的注意力功能:脑室内注射半胱氨酸、毒扁豆碱、基底前脑损伤及皮质内移植对多项选择连续反应时任务的影响。
Exp Brain Res. 1992;89(3):611-22. doi: 10.1007/BF00229886.