Influence of benzodiazepine binding site ligands on fear-conditioned contextual memory.

Influence of benzodiazepine binding site ligands on fear-conditioned contextual memory.
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苯二氮卓结合位点配体对恐惧条件情境记忆的影响。

DOI:
10.1016/s0014-2999(01)01199-2
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发表时间:
2001
影响因子:
5
通讯作者:
Loew,GH
Loew,GH
中科院分区:
医学2区
文献类型:
--
作者:
DeLorey,TM;Lin,RC;McBrady,B;He,X;Cook,JM;Lameh,J;Loew,GH

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评估了与γ-氨基丁酸A(GABAA)受体上的苯二氮卓类结合位点结合的八种化合物对情境记忆的影响,情境记忆是包括阿尔茨海默病在内的各种认知障碍中受影响的记忆的一个方面。使用巴甫洛夫恐惧条件反射范式,在C57 B1/6小鼠中评价每种配体对背景记忆的直接影响以及配体是否可以减弱东莨菪碱诱导的背景记忆损伤。在测试的八种配体中,一种受损的上下文记忆(激动剂),六种减弱东莨菪碱诱导的上下文记忆损伤(反向激动剂),并且一种拮抗反向激动剂减弱东莨菪碱诱导的上下文记忆损伤的能力。因此,进一步证明了苯二氮卓类结合位点配体能够对记忆调节施加双向影响。这项研究作为一个最初的出发点,在开发的药理学工具,用于破译GABA受体如何影响上下文记忆。
Eight compounds that bind to the benzodiazepine binding site on the γ-amino butyric acidA(GABAA) receptor were assessed for their influence on contextual memory, an aspect of memory affected in various cognitive disorders including Alzheimer's disease. Using a Pavlovian fear-conditioning paradigm, each ligand was evaluated in C57Bl/6 mice in regards to its direct affect on contextual memory and whether the ligand could attenuate scopolamine-induced contextual memory impairment. Of the eight ligands tested, one impaired contextual memory (agonist), six attenuated scopolamine-induced contextual memory impairment (inverse agonists), and one antagonized the ability of an inverse agonist to attenuate scopolamine-induced contextual memory impairment. Hence, further demonstrating the bi-directional influence benzodiazepine binding site ligands are able to exert on memory modulation. This study serves as an initial starting point in the development of pharmacological tools to be used in deciphering how GABAAreceptors influence contextual memory.
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