Li Song, Murakami Yukihisa, Wang Minwei, Maeda Kozo, Matsumoto Kinzo
Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Pharmacol Biochem Behav. 2006 Oct;85(2):324-31. doi: 10.1016/j.pbb.2006.08.015. Epub 2006 Oct 10.
To better understand neurochemical and psychopharmacological aspects of post-traumatic stress disorder (PTSD), it is necessary establish an animal model of PTSD in which behavioral changes persist for a long time after the initial traumatization. The present study aimed to characterize long-term behavioral alterations in male ICR mice as an animal model of PTSD consisting of a 2-day foot shock (0.8 mA, 10 s) followed by 3 weekly situational reminders (SR), and to evaluate the effects of repeated administration of valproate and diazepam on behavioral deficits of this animal model. The results showed that the aversive procedure induced several long-term behavioral deficiencies: increased freezing behavior and anxiety level, reduced time spent in an aversive like context. Repeated treatment with valproate (100-400 mg/kg, i.p.) induced a dose-dependent reduction of these behavioral changes. In contrast, diazepam at a low dose (0.25 mg/kg) but not at a high dose (4 mg/kg) reduced the behavioral deficiencies. These results demonstrate that exposure to intense foot shock associated with repeated situational reminders elicits long-term disturbances that last about 4 weeks after the foot shock exposure. These behavioral deficits can be ameliorated by repeated administration of valproate or diazepam at some special dose ranges.
为了更好地理解创伤后应激障碍（PTSD）的神经化学和精神药理学方面，有必要建立一种PTSD动物模型，其中行为变化在初始创伤后会长期持续。本研究旨在将雄性ICR小鼠的长期行为改变表征为PTSD动物模型，该模型包括为期2天的足部电击（0.8 mA，10秒），随后每周进行3次情境提醒（SR），并评估重复给予丙戊酸盐和地西泮对该动物模型行为缺陷的影响。结果表明，厌恶程序诱发了几种长期行为缺陷：僵住行为增加、焦虑水平升高、在类似厌恶情境中花费的时间减少。丙戊酸盐（100 - 400 mg/kg，腹腔注射）重复治疗导致这些行为变化呈剂量依赖性减少。相比之下，低剂量（0.25 mg/kg）而非高剂量（4 mg/kg）的地西泮减少了行为缺陷。这些结果表明，与重复情境提醒相关的强烈足部电击暴露会引发长期干扰，在足部电击暴露后持续约4周。在某些特定剂量范围内，重复给予丙戊酸盐或地西泮可改善这些行为缺陷。
