Zethof T J, Van der Heyden J A, Tolboom J T, Olivier B
Department of CNS Pharmacology, Solvay Duphar B.V., Weesp, Netherlands.
Eur J Pharmacol. 1995 Dec 27;294(1):125-35. doi: 10.1016/0014-2999(95)00520-x.
In group-housed mice (ten per cage), mice removed last from their home cage always have higher rectal temperatures than mice removed first from this cage. Stress-induced hyperthermia is calculated as the difference (delta T) between the basal temperature (mouse number 1) and the end temperature (mouse number 10) when the temperature of the ten mice is sequentially measured using a 1-min interval between rectal measurements. Using this protocol, various drugs, belonging to different pharmacological classes, were tested in order to investigate their putative anxiolytic effect, measured as a decrease in delta T. Benzodiazepines (diazepam, alprazolam), alcohol, and some (flesinoxan, buspirone), but not all (ipsapirone) 5-HT1A receptor agonists had anxiolytic properties with this protocol. Clonidine (alpha 2-adrenoceptor agonist) and prazosine (alpha 1-adrenoceptor antagonist) had, but at high doses, some anxiolytic actions. Antidepressants (desipramine, fluvoxamine, nomifensine, tianeptine, amitriptyline, clomipramine, imipramine), serotonergic ligands (ondansetron, ketanserin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine, metachlorophenylpiperazine (mCPP), eltoprazine) and various other drugs (phenobarbital, pentetrazol, haloperidol, apomorphine, amphetamine, (+)-N-[1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3( R)-yl]- N'-(3-methylphenyl)urea (MSD 365260), dizocilpine and acetyl salicylic acid) had no anxiolytic activity. The stress-induced hyperthermia protocol used was unable to detect anxiogenic properties of drugs, probably due to a (physiological) ceiling in the maximal end temperature. The stress-induced hyperthermia protocol with mice can be used to measure anxiolytic properties of drugs and is a fast and robust model which does not need extensive training of animals.
在群居小鼠（每笼10只）中，最后从其饲养笼中移出的小鼠直肠温度总是高于最先从该笼中移出的小鼠。应激诱导的体温过高通过基础体温（第1只小鼠）与最终体温（第10只小鼠）之间的差值（ΔT）来计算，测量这10只小鼠的体温时，直肠测量之间的间隔为1分钟。使用该方案，对属于不同药理学类别的各种药物进行了测试，以研究它们假定的抗焦虑作用，以ΔT的降低来衡量。苯二氮䓬类药物（地西泮、阿普唑仑）、酒精以及一些（氟司必林、丁螺环酮）但并非所有（伊沙匹隆）5-HT1A受体激动剂在此方案下具有抗焦虑特性。可乐定（α2肾上腺素能受体激动剂）和哌唑嗪（α1肾上腺素能受体拮抗剂）具有抗焦虑作用，但仅在高剂量时。抗抑郁药（地昔帕明、氟伏沙明、诺米芬辛、噻奈普汀、阿米替林、氯米帕明、丙咪嗪）、血清素能配体（昂丹司琼、酮色林、1-(2,5-二甲氧基-4-碘苯基)-2-氨基丙烷（DOI）、芬氟拉明、间氯苯哌嗪（mCPP）、依托普拉嗪）以及各种其他药物（苯巴比妥、戊四氮、氟哌啶醇、阿扑吗啡、苯丙胺、(+)-N-[1-甲基-2-氧代-5-苯基-2,3-二氢-1H-1,4-苯并二氮杂䓬-3(R)-基]-N'-(3-甲基苯基)脲（MSD 365260）、地佐环平、乙酰水杨酸）没有抗焦虑活性。所使用的应激诱导体温过高方案无法检测出药物的致焦虑特性，这可能是由于最高最终体温存在（生理）上限。小鼠应激诱导体温过高方案可用于测量药物的抗焦虑特性，是一种快速且可靠的模型，无需对动物进行广泛训练。
