Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto CEP:14049-900, Brazil.
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto CEP:14049-900, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Feb 2;81:178-186. doi: 10.1016/j.pnpbp.2017.10.018. Epub 2017 Oct 28.
Exposure to elevated concentrations of CO or hypoxia has been widely used in psychiatric research as a panic provoking stimulus. However, the use of these respiratory challenges to model panic-like responses in experimental animals has been less straightforward. Little data is available, from behavioral and endocrine perspectives, to support the conclusion that a marked aversive situation, such as that experienced during panic attacks, was evoked in these animals. We here compared the behavioral responses of male CB57BL/6 mice during exposure to 20% CO or 7% O and its consequence on plasma levels of corticosterone. We also evaluated whether clinically-effective panicolytic drugs affect the behavioral responses expressed during CO exposure. The results showed that whereas hypoxia caused a marked reduction in locomotion, inhalation of CO-enriched air evoked an active escape response, characterized by bouts of upward leaps directed to the border of the experimental cage, interpreted as escape attempts. Corticosterone levels were increased 30min after either of the respiratory challenges used, but it was higher in the hypoxia group. Chronic (21days), but not acute, treatment with fluoxetine or imipramine (5, 10 or 15mg/kg) or a single injection of alprazolam (0.025, 0.05 or 0.1mg/kg), but not of the anxiolytic diazepam (0.025, 0.05 or 0.1 and 1mg/kg) reduced the number of escape attempts, indicating a panicolytic-like effect. Altogether, the results suggest that whereas hypoxia increased anxiety, exposure to 20% CO evoked a panic-like state. The latter condition/test protocol seems to be a simple and validated model for studying in mice pathophysiological mechanisms and the screening of novel drugs for panic disorder.
暴露于高浓度的 CO 或缺氧已被广泛应用于精神病学研究中，作为引发惊恐的刺激物。然而，将这些呼吸挑战用于实验动物模型中的惊恐样反应的应用并不那么直接。从行为和内分泌的角度来看，很少有数据支持这样的结论，即这些动物经历了一种明显的厌恶情况，如惊恐发作期间所经历的情况。在这里，我们比较了雄性 CB57BL/6 小鼠在暴露于 20% CO 或 7% O 时的行为反应及其对血浆皮质酮水平的影响。我们还评估了临床有效的抗惊恐药物是否会影响 CO 暴露期间表达的行为反应。结果表明，虽然缺氧导致运动明显减少，但吸入富含 CO 的空气会引起积极的逃避反应，表现为向上跳跃冲向实验笼的边缘，被解释为逃避尝试。在使用的两种呼吸挑战后 30 分钟，皮质酮水平升高，但在缺氧组中更高。慢性（21 天）而非急性，用氟西汀或丙咪嗪（5、10 或 15mg/kg）或单次注射阿普唑仑（0.025、0.05 或 0.1mg/kg）治疗，但不是用苯二氮䓬类药物（地西泮 0.025、0.05 或 0.1 和 1mg/kg）减少了逃避尝试的次数，表明具有抗惊恐样作用。总之，结果表明，虽然缺氧增加了焦虑，但暴露于 20% CO 会引起惊恐样状态。后一种情况/测试方案似乎是研究小鼠病理生理机制和筛选新的惊恐障碍药物的简单而有效的模型。
