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麻醉雌性大鼠在新生儿期母婴分离后发生高碳酸血症通气反应:对惊恐发作起源的深入了解?

Hypercapnic ventilatory response of anesthetized female rats subjected to neonatal maternal separation: insight into the origins of panic attacks?

机构信息

Department of Pediatrics, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada.

出版信息

Respir Physiol Neurobiol. 2011 Feb 15;175(2):288-95. doi: 10.1016/j.resp.2010.12.004. Epub 2010 Dec 13.

DOI:10.1016/j.resp.2010.12.004
PMID:21147276
Abstract

Neonatal maternal separation (NMS) is a form of stress that interferes with the regulation of the stress response, an effect that predisposes to the emergence of panic and anxiety related disorders. We previously showed that at adulthood, awake female (but not male) rats subjected to NMS show a hypercapnic ventilatory response (HCVR; 5% CO2) that is 63% greater than controls (Genest et al., 2007). To understand the mechanisms underlying the sex-specific effects of NMS on the ventilatory response to CO2, we used two different anesthetized female rat preparations to assess central CO2 chemosensitivity and contribution of sensory afferents (stretch receptors and peripheral chemoreceptors) that influence the HCVR. Data show that anesthesia eliminated the respiratory phenotype observed previously in awake females and CO2 chemosensitivity did not differ between groups. Finally, the assessment of the ovarian hormone levels across the oestrus cycle failed to reveal significant differences between groups. Since anesthesia did not affect the manifestation of NMS-related respiratory dysfunction in males (including the hypercapnic ventilatory response) (Kinkead et al., 2005; Dumont and Kinkead, 2010), we propose that the panic or anxiety induced by CO2 during wakefulness is responsible for enhancement of the HCVR in NMS females.

摘要

新生儿母婴分离(NMS)是一种干扰应激反应调节的应激形式,这种效应使动物易患与恐慌和焦虑相关的障碍。我们之前的研究表明,在成年期,经历 NMS 的清醒雌性(而非雄性)大鼠的高碳酸血症通气反应(HCVR;5% CO2)比对照组高 63%(Genest 等人,2007 年)。为了了解 NMS 对 CO2 通气反应的性别特异性影响的机制,我们使用两种不同的麻醉雌性大鼠制备物来评估中枢 CO2 化学敏感性以及影响 HCVR 的感觉传入(伸展感受器和外周化学感受器)的贡献。数据表明,麻醉消除了在清醒雌性大鼠中观察到的先前的呼吸表型,并且两组之间的 CO2 化学敏感性没有差异。最后,对发情周期中卵巢激素水平的评估未能显示组间存在显著差异。由于麻醉并未影响雄性大鼠中与 NMS 相关的呼吸功能障碍的表现(包括高碳酸血症通气反应)(Kinkead 等人,2005 年;Dumont 和 Kinkead,2010 年),我们提出,在清醒状态下 CO2 引起的恐慌或焦虑是导致 NMS 雌性大鼠 HCVR 增强的原因。

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