Withdrawal from progesterone increases expression of α4, β1, and δ GABAA receptor subunits in neurons in the periaqueductal gray matter in female Wistar rats
Withdrawal from progesterone increases expression of α4, β1, and δ GABAA receptor subunits in neurons in the periaqueductal gray matter in female Wistar rats
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DOI：
10.1002/cne.20540
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发表时间：
2005-05-23
影响因子：
2.5
通讯作者：
Lovick, T
中科院分区：
文献类型：
--
作者：
Griffiths, J;Lovick, T
经前焦虑障碍（PMDD）与其他精神疾病如惊恐障碍（PD）共病。这两种情况的症状在月经周期的黄体晚期加重，此时孕酮水平急剧下降。本研究探讨了孕激素戒断（PWD）对成年雌性Wistar大鼠中脑导水管周围灰质（PAG）惊恐回路内神经元α 4、β 1和δ GABA（A）受体亚单位表达的影响。在溶剂处理动物（VEH）、停止黄体酮给药方案24小时后的大鼠（PWD，5 mg kg（-1）i. p.每天两次，持续6天）和维持黄体酮7天（HP）的动物中，α 4、β 1和8 GABAA受体亚基的免疫染色存在于整个PAG的神经元中。与HP和VEH动物相比，它们彼此之间没有显著差异，PWD大鼠PAG中存在的免疫染色神经元的数量显著较高。该效应在PAG的背外侧柱中最为明显。三种GABAA受体亚单位的平行变化表明孕酮水平下降可能与α 4 β 1 δ亚型新受体的表达有关。这可能导致PAG内GABA能传递的功能变化。我们认为，GABA的变化，受体介导的抑制性音调的PAG随之退出孕酮可能有助于增加焦虑和恐慌的易感性，在月经周期的黄体晚期PMDD和PD患者。(c)2005 Wiley-Liss，Inc.
Premenstrual dysphoric disorder (PMDD) shows comorbidity with other psychiatric conditions such as panic disorder (PD). The symptoms of both conditions are exacerbated during the late luteal phase of the menstrual cycle, when progesterone levels fall sharply. The present study investigated the effect of withdrawal from progesterone (PWD) on expression of alpha 4, beta 1, and delta GABA(A) receptor subunits in neurons within the panic circuitry of the midbrain periaqueductal gray matter (PAG) in adult female Wistar rats. Immunostaining for alpha 4, beta 1, and 8 GABAA receptor subunits was present in neurons throughout the PAG in vehicle-treated animals (VEH), in rats after 24 hours withdrawal from a progesterone dosing regime (PWD, 5 mg kg(-1) i.p. twice daily for 6 days), and in animals maintained on progesterone for 7 days (HP). Compared to HP and VEH animals, which did not differ significantly from each other, the number of immunostained neurons present in the PAG of PWD rats was significantly higher. The effect was most pronounced in the dorsolateral column of the PAG. The parallel changes in the three GABAA receptor subunits suggests that falling progesterone levels may be associated with expression of new receptors of the alpha 4 beta 1 delta subtype. This could lead to functional changes in GABAergic transmission within the PAG. We suggest that changes in GABA, receptor-mediated inhibitory tone in the PAG consequent to withdrawal from progesterone may contribute to the increased anxiety and susceptibility to panic seen during the late luteal phase of the menstrual cycle in PMDD and PD patients. (c) 2005 Wiley-Liss, Inc.