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慢性抗抑郁药治疗对大鼠极端焦虑新模型的疗效

Efficacy of chronic antidepressant treatments in a new model of extreme anxiety in rats.

作者信息

Javelot Hervé, Weiner Luisa, Terramorsi Roxane, Rougeot Catherine, Lalonde Robert, Messaoudi Michaël

机构信息

Neuropsychopharmacology Department, ETAP-Applied Ethology, 54500 Vandoeuvre-lés-Nancy, France.

出版信息

Depress Res Treat. 2011;2011:531435. doi: 10.1155/2011/531435. Epub 2011 Jul 26.

Abstract

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders.

摘要

在人类中发现的焦虑症动物模型,如恐慌症和创伤后应激障碍,通常包括引发逃避和回避行为的自发和条件性恐惧。具有学习成分的恐慌症模型的建立应能增加对焦虑症相关机制的了解。在我们的大鼠极端焦虑行为学模型中,在无法逃避的情况下将强迫性呼吸暂停与冷水蒸发相结合。根据赋形剂对照组的反应,阵发性恐惧所涉及的行为是被动(僵住)和主动(跳跃)反应。我们的结果表明,亚慢性给予氟西汀(5毫克/千克,腹腔注射,21天)和丙咪嗪(10毫克/千克,腹腔注射,14天)可减轻僵住和跳跃行为,而急性给予氟西汀(1毫克/千克,腹腔注射)则产生相反的效果。急性低剂量地西泮(1毫克/千克,腹腔注射)无效,而较高剂量的3毫克/千克,腹腔注射,以及氯硝西泮(1毫克/千克,腹腔注射)仅对跳跃有影响。因此,在这种实验条件下产生的阵发性恐惧可能模拟了焦虑症患者中观察到的症状。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4747/3144710/383f5a104b2d/DRT2011-531435.001.jpg

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