Vinkers Christiaan H, van Bogaert Meg J V, Klanker Marianne, Korte S Mechiel, Oosting Ronald, Hanania Taleen, Hopkins Seth C, Olivier Berend, Groenink Lucianne
Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS) and Rudolf Magnus Institute of Neuroscience, Utrecht University, Sorbonnelaan 16, 3584 CA Utrecht, The Netherlands.
Eur J Pharmacol. 2008 May 13;585(2-3):407-25. doi: 10.1016/j.ejphar.2008.02.097. Epub 2008 Mar 18.
In anxiety research, the search for models with sufficient clinical predictive validity to support the translation of animal studies on anxiolytic drugs to clinical research is often challenging. This review describes the stress-induced hyperthermia (SIH) paradigm, a model that studies the activation of the autonomic nervous system in response to stress by measuring body temperature. The reproducible and robust SIH response, combined with ease of testing, make the SIH paradigm very suitable for drug screening. We will review the current knowledge on the neurobiology of the SIH response, discuss the role of GABA(A) and serotonin (5-HT) pharmacology, as well as how the SIH response relates to infectious fever. Furthermore, we will present novel data on the SIH response variance across different mice and their sensitivity to anxiolytic drugs. The SIH response is an autonomic stress response that can be successfully studied at the level of its physiology, pharmacology, neurobiology and genetics and possesses excellent animal-to-human translational properties.
在焦虑症研究中，寻找具有足够临床预测效度以支持将抗焦虑药物的动物研究成果转化为临床研究的模型往往具有挑战性。本综述介绍了应激诱导体温过高（SIH）范式，该模型通过测量体温来研究自主神经系统对应激的激活情况。可重复且稳定的SIH反应，加上测试简便，使得SIH范式非常适合药物筛选。我们将回顾关于SIH反应神经生物学的现有知识，讨论γ-氨基丁酸A（GABA(A)）和血清素（5-HT）药理学的作用，以及SIH反应与感染性发热的关系。此外，我们将展示不同小鼠之间SIH反应差异及其对抗焦虑药物敏感性的新数据。SIH反应是一种自主应激反应，可以在其生理学、药理学、神经生物学和遗传学层面成功开展研究，并且具有出色的从动物到人类的转化特性。
