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恐惧增强的惊吓反应,而不是光增强的惊吓反应,会被焦虑药物增强。

Fear-potentiated startle, but not light-enhanced startle, is enhanced by anxiogenic drugs.

机构信息

Section Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.

出版信息

Pharmacol Biochem Behav. 2010 Jul;96(1):24-31. doi: 10.1016/j.pbb.2010.04.002. Epub 2010 Apr 13.

Abstract

RATIONALE AND OBJECTIVES

The light-enhanced startle paradigm (LES) is suggested to model anxiety, because of the non-specific cue and the long-term effect. In contrast, the fear-potentiated startle (FPS) is suggested to model conditioned fear. However, the pharmacological profiles of these two paradigms are very similar. The present study investigated the effects of putative anxiogenic drugs on LES and FPS and aimed at determining the sensitivity of LES for anxiogenic drugs and to potentially showing a pharmacological differentiation between these two paradigms.

METHODS

Male Wistar rats received each dose of the alpha(2)-adrenoceptor antagonist yohimbine (0.25-1.0mg/kg), the 5-HT(2C) receptor agonist m-chlorophenylpiperazine (mCPP, 0.5-2.0mg/kg) or the GABA(A) inverse receptor agonist pentylenetetrazole (PTZ, 3-30mg/kg) and were subsequently tested in either LES or FPS.

RESULTS

None of the drugs enhanced LES, whereas mCPP increased percentage FPS and yohimbine increased absolute FPS values. Furthermore, yohimbine increased baseline startle amplitude in the LES, while mCPP suppressed baseline startle in both the LES and FPS and PTZ suppressed baseline startle in the FPS.

CONCLUSIONS

In contrast to findings in the FPS paradigm, none of the drugs were able to exacerbate the LES response. Thus, a clear pharmacological differentiation was found between LES and FPS.

摘要

原理和目的

光增强惊跳范式(LES)被认为可用于模拟焦虑,因为其是非特异性线索和长期效应。相比之下,恐惧增强惊跳(FPS)被认为可用于模拟条件性恐惧。然而,这两种范式的药理学特征非常相似。本研究旨在调查潜在的焦虑药物对 LES 和 FPS 的影响,以确定 LES 对焦虑药物的敏感性,并有可能显示这两种范式之间的药理学差异。

方法

雄性 Wistar 大鼠接受了不同剂量的α2-肾上腺素能拮抗剂育亨宾(0.25-1.0mg/kg)、5-HT2C 受体激动剂 m-氯苯基哌嗪(mCPP,0.5-2.0mg/kg)或 GABA-A 反向受体激动剂戊四氮(PTZ,3-30mg/kg),随后在 LES 或 FPS 中进行测试。

结果

没有一种药物增强了 LES,而 mCPP 增加了百分比 FPS,育亨宾增加了绝对 FPS 值。此外,育亨宾增加了 LES 的基础惊跳幅度,而 mCPP 抑制了 LES 和 FPS 的基础惊跳,PTZ 抑制了 FPS 的基础惊跳。

结论

与 FPS 范式的发现相反,没有一种药物能够加剧 LES 反应。因此,在 LES 和 FPS 之间发现了明显的药理学差异。

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