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药物发现中的恐惧增强惊吓和光增强惊吓模型。

Fear-potentiated startle and light-enhanced startle models in drug discovery.

作者信息

Groenink Lucianne, Bijlsma Elisabeth Y, Olivier Berend

机构信息

Department of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute for Neuroscience, Utrecht University, Utrecht, The Netherlands.

出版信息

Curr Protoc Pharmacol. 2008 Jun;Chapter 5:Unit5.48. doi: 10.1002/0471141755.ph0548s41.

DOI:10.1002/0471141755.ph0548s41
PMID:22294228
Abstract

Described in this unit are the fear-potentiated startle (FPS) and light-enhanced startle (LES) tests. These protocols have proven reliable in detecting the anxiolytic properties of test compounds. The principle of these tests is that the magnitude of the acoustic startle reflex is an index of anxiety. The FPS test includes two training sessions in which an intrinsically aversive foot shock is paired with a neutral cue light. In the test session presentation of this cue light is subsequently used to elicit startle potentiation. In the LES test startle reactivity is increased by presentation of bright light. Because LES is based on the innate aversion of rodents for bright light it does not require training sessions. Although LES has been used less frequently than FPS for screening compounds, it has an advantage in that drug effects on startle potentiation are independent of memory retrieval. Further, the contextual anxiety measured in the LES test could be more relevant for pathological anxiety than the conditioned fear associated with the FPS test.

摘要

本单元介绍了恐惧增强惊吓(FPS)和光增强惊吓(LES)测试。这些实验方案已被证明在检测受试化合物的抗焦虑特性方面是可靠的。这些测试的原理是,听觉惊吓反射的幅度是焦虑的一个指标。FPS测试包括两个训练阶段,在这个过程中,一种内在厌恶的足部电击与一个中性提示光配对。在测试阶段,这个提示光的呈现随后被用来引发惊吓增强。在LES测试中,强光的呈现会增加惊吓反应性。因为LES基于啮齿动物对强光的先天厌恶,所以它不需要训练阶段。虽然LES在筛选化合物时比FPS使用得少,但它有一个优点,即药物对惊吓增强的影响与记忆检索无关。此外,LES测试中测量的情境性焦虑可能比与FPS测试相关的条件性恐惧与病理性焦虑更相关。

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