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在听觉惊吓范式中,对于基线“焦虑”水平较高的大鼠,急性艾司西酞普兰而非情境性条件作用会产生更强的“致焦虑”效应。

Acute escitalopram but not contextual conditioning exerts a stronger "anxiogenic" effect in rats with high baseline "anxiety" in the acoustic startle paradigm.

作者信息

Pettersson Robert, Näslund Jakob, Nilsson Staffan, Eriksson Elias, Hagsäter S Melker

机构信息

Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Box 431, SE-405 30, Gothenburg, Sweden.

出版信息

Psychopharmacology (Berl). 2015 Apr;232(8):1461-9. doi: 10.1007/s00213-014-3783-z. Epub 2014 Nov 25.

Abstract

RATIONALE

Acute administration of selective serotonin reuptake inhibitors (SSRIs) may enhance anxiety in humans, those with anxiety disorders being more susceptible than others. Fear-conditioned or unconditioned acoustic startle and freezing are common measures of fear and/or "anxiety" in rodents that may be used to study this effect of SSRIs preclinically.

OBJECTIVES

Our aim was to shed further light on the effect of acute administration of an SSRI, escitalopram (10 mg/kg), on startle and freezing in the absence or presence of prior contextual conditioning. Repeated testing also enabled us to evaluate (i) if there are stable inter-animal variations with respect to these parameters in a batch of outbred Wistar rats, (ii) the possible relationship between the two and (iii) if baseline behaviour predicts the response to escitalopram.

RESULTS

Inter-animal test-retest correlations were found for both startle and freezing at baseline, and the two parameters also correlated with each other. Both escitalopram and contextual conditioning increased freezing and startle but without exerting any synergistic effect. While animals displaying high startle at baseline showed higher susceptibility to respond to escitalopram, the effect of conditioning was more pronounced in those with low baseline startle.

CONCLUSIONS

The results support the usefulness of both conditioned and non-conditioned startle and freezing to capture an "anxiogenic" influence of SSRIs. Also, they suggest that baseline non-conditioned startle may predict this response in a manner reflecting the clinical situation in the sense that subjects with high baseline "anxiety" are particularly prone to respond with enhanced "anxiety" following acute SSRI administration.

摘要

理论依据

急性给予选择性5-羟色胺再摄取抑制剂(SSRI)可能会增强人类的焦虑感,焦虑症患者比其他人更易受影响。恐惧条件化或非条件化的听觉惊吓反应和僵住反应是啮齿动物中常见的恐惧和/或“焦虑”测量指标,可用于临床前研究SSRI的这种作用。

目的

我们的目的是进一步阐明急性给予SSRI艾司西酞普兰(10毫克/千克)在有无先前情境条件化的情况下对惊吓反应和僵住反应的影响。重复测试还使我们能够评估:(i)在一批远交系Wistar大鼠中,这些参数在动物个体间是否存在稳定的差异;(ii)两者之间可能的关系;(iii)基线行为是否能预测对艾司西酞普兰的反应。

结果

在基线时,动物个体间的惊吓反应和僵住反应的重测相关性均被发现,且这两个参数之间也相互关联。艾司西酞普兰和情境条件化均增加了僵住反应和惊吓反应,但未产生任何协同作用。虽然在基线时表现出高惊吓反应的动物对艾司西酞普兰的反应更敏感,但条件化的影响在基线惊吓反应低的动物中更为明显。

结论

结果支持条件化和非条件化的惊吓反应及僵住反应对于捕捉SSRI的“致焦虑”影响均有用。此外,结果表明基线非条件化惊吓反应可能以反映临床情况的方式预测这种反应,即基线“焦虑”高的受试者在急性给予SSRI后特别容易出现“焦虑”增强反应。

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