Interdisciplinary Program of Physiology, Graduate School, Chulalongkorn University, Thailand.
Behav Brain Res. 2013 Jun 1;246:86-93. doi: 10.1016/j.bbr.2013.03.008. Epub 2013 Mar 13.
Ovariectomized animals have frequently been used to study the effects of estrogen deficiency on mood disorders, particularly anxiety disorder. However, a range of results including anxiolytic, anxiogenic, and no behavioral effects have been reported. One discrepancy was the different in behavioral testing time following ovariectomized; therefore, the aim of this study was to examine the effects of time of estrogen deprivation on anxiety-like behavior and on GABAA receptor subunit gene expressions in ovariectomized rats. The GABAA receptor was of special interest as it had been shown to be influenced by estrogen. In this study, adult female Wistar rats were ovariectomized and randomly assigned into 2 groups: ovariectomized-rat (Ovx) and ovariectomized-rat treated with estrogen (E2) at the dosage of 1μg/kg BW. At 7, 14, 21 and 28 days after ovariectomy, the rats were tested with elevated T-maze (ETM) and open field. We found that after ovariectomy, the Ovx showed signs of anxiety as demonstrated by the increased in inhibitory avoidance latency in the ETM with significant effect at day 21 and even higher at day 28. On the other hand, the escape latency was not differed between each time point. These behavioral data implied that the anxiety in term of generalized anxiety disorder as interpreted from impaired inhibitory avoidance in the ETM was affected by estrogen depletion; while, the anxiety disorder in term of panic disorder as shown by escape latency was unaffected. For gene expression analysis, the GABAA receptor α2-, α3- and α4-subunits in Ovx groups were significantly increased in the midbrain compared to E2 groups; whereas, in the amygdala, the gene expressions were not different between Ovx and E2 groups. In conclusion, these results indicated that ovariectomized as early as 21 day can induce anxiety and the altered GABAA receptor subunit may be partially responsible for anxiety following estrogen deprivation.
去卵巢动物常用于研究雌激素缺乏对情绪障碍的影响，特别是焦虑障碍。然而，已经报道了一系列结果，包括抗焦虑、致焦虑和无行为影响。一个差异是去卵巢后进行行为测试的时间不同；因此，本研究旨在研究雌激素剥夺对去卵巢大鼠焦虑样行为和 GABAA 受体亚基基因表达的影响。GABAA 受体是特别感兴趣的，因为它已经显示受雌激素影响。在这项研究中，成年雌性 Wistar 大鼠被去卵巢，并随机分为 2 组：去卵巢大鼠（Ovx）和用 1μg/kg BW 的雌激素（E2）处理的去卵巢大鼠。在去卵巢后 7、14、21 和 28 天，大鼠进行高架 T 迷宫（ETM）和旷场测试。我们发现，去卵巢后，Ovx 表现出焦虑迹象，如 ETM 中的抑制回避潜伏期增加，在第 21 天有显著影响，甚至在第 28 天更高。另一方面，每个时间点的逃逸潜伏期没有差异。这些行为数据表明，广义焦虑障碍的焦虑（解释为 ETM 中抑制回避受损）受雌激素耗竭的影响；而恐慌障碍的焦虑（如逃逸潜伏期所示）不受影响。对于基因表达分析，与 E2 组相比，Ovx 组的中脑中 GABAA 受体 α2、α3 和 α4 亚基的基因表达显著增加；而在杏仁核中，Ovx 和 E2 组之间的基因表达没有差异。总之，这些结果表明，早在 21 天去卵巢就可以引起焦虑，改变的 GABAA 受体亚基可能部分负责雌激素缺乏后的焦虑。
