Benzodiazepines have no effect on fear-potentiated startle in humans
Benzodiazepines have no effect on fear-potentiated startle in humans
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DOI：
10.1007/s00213-002-1011-8
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发表时间：
2002-05-01
影响因子：
3.4
通讯作者：
Verbaten, MN
中科院分区：
文献类型：
--
作者：
Baas, JMP;Grillon, C;Verbaten, MN
理论基础：临床前和临床研究已经提供了大量证据，表明恐惧强化的惊吓范式代表了客观评估焦虑和恐惧情绪状态的有效模型。目的：本报告中提出的四项研究试图通过检测苯二氮类药物对基线惊吓和恐惧惊吓的影响，进一步验证“休克威胁”范式作为人类对恐惧强化惊吓的类比。方法：在乌得勒支大学进行了三项研究，评估了奥西潘和安定对基线和恐惧增强型惊吓的影响，而在耶鲁大学进行的第四项研究，评估了安定对基线、背景和特定的恐惧增强型惊吓的影响。电击威胁范式包括关于两个视觉线索的口头指导(威胁线索预测可能发生电击，另一个预测安全时间)，然后对这些线索进行一系列呈现。在这些条件下，为了引起惊吓反应，提出了声学惊吓刺激。惊吓反应的大小被用来指示在威胁和安全期间经历的恐惧或警报的程度。第四项研究考察了在类似的休克威胁模式下静脉注射安定的效果，除了有两个额外的背景操作：电极放置和黑暗。结果：不同的药物操作均不影响惊吓的特异性威胁线索增强。然而，观察到基线惊厥的减少。此外，安定可抑制黑暗的惊吓增强作用。结论：至少有一种类型的恐惧强化惊吓，即通过线索特异性恐惧操作而增强，对苯二氮卓类药物治疗不敏感。相比之下，更类似于焦虑的操作(黑暗、背景)的影响似乎对苯二氮卓类药物敏感。需要人类实验模型区分这些线索特定的反应和背景反应，以更好地阐明焦虑症的解剖学和药理学上的差异。
Rationale: Pre-clinical and clinical investigations have provided a great deal of evidence that the fear-potentiated startle paradigm represents a valid model for the objective assessment of emotional states of anxiety and fear. Objective: The four studies presented in this report sought to further validate the "threat of shock" paradigm as a human analogue to fear-potentiated startle in rats, by examining the effect of benzodiazepine administration on both baseline and fear-potentiated startle. Methods: Three studies, conducted at Utrecht University, evaluated the effects of oxazepam and of diazepam on baseline and fear-potentiated startle, whereas a fourth study, conducted at Yale University, evaluated the effect of diazepam on baseline, contextual and cuespecific fear-potentiated startle. The threat of shock paradigm consisted of verbal instruction about two visual cues (the threat cue predicted the possible administration of electric shock, the other predicted a safe period), followed by a series of presentations of these cues. During these conditions, acoustic startle stimuli were presented in order to elicit startle responses. The magnitude of the startle response was used to index the degree of fear or alarm experienced during the periods of threat and safety. The fourth study examined the effect of IV administration of diazepam in a similar threat of shock paradigm except that there were two additional context manipulations: electrode placement and darkness. Results: None of the drug manipulations affected specific threat-cue potentiation of startle. However, reductions in baseline startle were observed. Further, startle potentiation by darkness was inhibited by diazepam. Conclusions: At least one type of fear-potentiated startle, i.e. potentiation by a cue-specific fear manipulation, is not susceptible to benzodiazepine treatment. In contrast, effects of manipulations more akin to anxiety (darkness, context) appear sensitive to benzodiazepines. Human experimental models differentiating between these cue specific and contextual responses are needed to shed more light on differences in the anatomy and pharmacology of anxiety disorders.