Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
Neurosci Biobehav Rev. 2014 Oct;46 Pt 3:465-71. doi: 10.1016/j.neubiorev.2014.03.006. Epub 2014 Apr 3.
Panic disorder is twice a common in women than in men. In women, susceptibility to panic increases during the late luteal (premenstrual) phase of the menstrual cycle, when progesterone secretion is in rapid decline. This article considers the evidence for the midbrain periaqueductal grey (PAG) as a locus for panic and for the use of PAG stimulation as an animal model of panic in both sexes. We show in females how a rapid fall in progesterone secretion, such as occurs during the late dioestrus phase of the ovarian cycle in rats (similar to the late luteal phase in women), triggers a neuronal withdrawal response during which the excitability of the midbrain panic circuitry increases as a result of upregulation of extrasynaptic GABAA receptors on inhibitory interneurones in the PAG. The withdrawal effect is due not to the native hormone but to its neuroactive metabolite allopregnanolone. Differences in the kinetics of allopregnanolone metabolism may contribute to individual differences in susceptibility to panic in women.
惊恐障碍在女性中的发病率是男性的两倍。女性在月经周期的黄体后期（经前期），即孕酮分泌迅速下降时，易患惊恐障碍。本文探讨了中脑导水管周围灰质（periaqueductal grey，PAG）作为惊恐发作的一个病灶的证据，以及 PAG 刺激在两性中作为惊恐动物模型的应用。我们在雌性动物中展示了孕酮分泌的迅速下降（如在大鼠卵巢周期的晚期发情期发生的情况，类似于女性的黄体后期）如何引发神经元撤退反应，在此期间，由于 PAG 中的抑制性中间神经元上的突触外 GABAA 受体的上调，中脑惊恐回路的兴奋性增加。撤退效应不是由天然激素引起的，而是由其神经活性代谢物别孕烯醇酮引起的。别孕烯醇酮代谢的动力学差异可能导致女性惊恐易感性的个体差异。
