Olivier Berend, Zethof Theo, Pattij Tommy, van Boogaert Meg, van Oorschot Ruud, Leahy Christina, Oosting Ronald, Bouwknecht Arjan, Veening Jan, van der Gugten Jan, Groenink Lucianne
Department of Psychopharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, The Netherlands.
Eur J Pharmacol. 2003 Feb 28;463(1-3):117-32. doi: 10.1016/s0014-2999(03)01326-8.
When mammals, including man, are confronted with a stressful event, their core body temperature rises, stress-induced hyperthermia. In mice, the stress-induced hyperthermia procedure has been developed to measure antistress or anxiolytic-like effects of psychoactive drugs. Group-housed and singly housed versions of the stress-induced hyperthermia generate comparable results. Because the number of animals needed to perform an experiment is much lower in the singly housed versus the group-housed procedure, the former is the test of choice for pharmacological testing. A typical stress-induced hyperthermia test starts with an injection 60 min before the first rectal temperature measurement (T(1)), followed by a second temperature measurement (T(2)) 10-15 min later. The difference DeltaT (=T(2)-T(1)) is the stress-induced hyperthermia. The procedure also measures the intrinsic activity of drugs on the basal body temperature and DeltaT is relatively independent from the intrinsic temperature effects of drugs. Anxiolytic drugs (benzodiazepines, 5-HT(1A) receptor agonists, alcohol) reduce DeltaT suggestive of anxiolytic-like effects. Because the parameter measured for anxiety in the stress-induced hyperthermia procedure is not dependent on locomotor activity, like in almost all other anxiety tests, the stress-induced hyperthermia procedure is an attractive addition to tests in the anxiety field. Because the stress-induced hyperthermia is also present with a comparable pharmacological profile in females, this procedure has a wide species and gender validity. The procedure was applied in various genetically modified mice [5-HT(1A) and 5-HT(1B) receptor knockout (KO) mice and corticotropin-releasing hormone overexpressing (CRH-OE) mice] to study phenotypic influences of the various mutations on aspects of anxiety. The stress-induced hyperthermia test in singly housed male and female mice appears a useful and extremely simple test to measure effects of drugs on certain aspects of anxiety or to help to determine phenotypic differences in mutant mice.
当包括人类在内的哺乳动物面临压力事件时，其核心体温会升高，即应激性体温过高。在小鼠中，应激性体温过高程序已被开发出来，用于测量精神活性药物的抗应激或抗焦虑样作用。应激性体温过高的群居和独居版本产生的结果相当。由于与群居程序相比，进行实验所需的动物数量在独居程序中要少得多，所以前者是药理学测试的首选试验。典型的应激性体温过高测试在第一次直肠温度测量（T(1)）前60分钟开始注射，随后在10 - 15分钟后进行第二次温度测量（T(2)）。差值ΔT（=T(2)-T(1)）就是应激性体温过高。该程序还能测量药物对基础体温的内在活性，并且ΔT相对独立于药物的内在温度效应。抗焦虑药物（苯二氮䓬类、5 - HT(1A)受体激动剂、酒精）会降低ΔT，提示有抗焦虑样作用。由于在应激性体温过高程序中用于测量焦虑的参数不像几乎所有其他焦虑测试那样依赖于运动活动，所以应激性体温过高程序是焦虑领域测试中一个有吸引力的补充。由于雌性动物中也存在具有类似药理学特征的应激性体温过高，所以该程序具有广泛的物种和性别有效性。该程序已应用于各种基因改造小鼠（5 - HT(1A)和5 - HT(1B)受体敲除（KO）小鼠以及促肾上腺皮质激素释放激素过表达（CRH - OE）小鼠），以研究各种突变对焦虑方面的表型影响。在独居的雄性和雌性小鼠中进行的应激性体温过高测试似乎是一种有用且极其简单的测试，可用于测量药物对焦虑某些方面的影响，或有助于确定突变小鼠的表型差异。
