BACKGROUND Estrogen increases dramatically during pregnancy but quickly drops below prepregnancy levels at birth and remains suppressed during the postpartum period. Clinical and rodent work suggests that this postpartum drop in estrogen results in an estrogen withdrawal state that is related to changes in affect, mood, and behavior. How estrogen withdrawal affects oxytocin (OT) neurocircuitry has not been examined. METHODS We used a hormone-simulated pseudopregnancy followed by estrogen withdrawal in Syrian hamsters, a first for this species. Ovariectomized females were given daily injections to approximate hormone levels during gestation and then withdrawn from estrogen to simulate postpartum estrogen withdrawal. These hamsters were tested for behavioral assays of anxiety and anhedonia during estrogen withdrawal. Neuroplasticity in OT-producing neurons in the paraventricular nucleus of the hypothalamus and its efferent targets was measured. RESULTS Estrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus maze and open field tests but did not differ from control females in sucrose preference. Furthermore, estrogen-withdrawn females had more OT-immunoreactive cells and OT messenger RNA in the paraventricular nucleus of the hypothalamus and an increase in OT receptor density in the dorsal raphe nucleus. Finally, blocking OT receptors in the dorsal raphe nucleus during estrogen withdrawal prevented the high-anxiety behavioral phenotype in estrogen-withdrawn females. CONCLUSIONS Estrogen withdrawal induces OT neuroplasticity in the paraventricular nucleus of the hypothalamus and dorsal raphe nucleus to increase anxiety-like behavior during the postpartum period. More broadly, these experiments suggest Syrian hamsters as a novel organism in which to model the effects of postpartum estrogen withdrawal on the brain and anxiety-like behavior.

中文翻译：

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雌激素戒断通过室旁下丘脑和中缝背核的催产素可塑性增加产后焦虑


背景技术雌激素在怀孕期间急剧增加，但在出生时迅速降至怀孕前水平以下，并在产后期间保持抑制状态。临床和啮齿动物研究表明，产后雌激素下降会导致雌激素戒断状态，这与情感、情绪和行为的变化有关。雌激素戒断如何影响催产素 (OT) 神经回路尚未得到研究。方法 我们对叙利亚仓鼠进行了激素模拟假怀孕，然后雌激素撤退，这对于该物种来说是首次。切除卵巢的雌性在妊娠期间每天接受注射以接近激素水平，然后撤回雌激素以模拟产后雌激素撤退。这些仓鼠在雌激素戒断期间进行了焦虑和快感缺乏的行为分析。测量了下丘脑室旁核及其传出靶标中产生 OT 的神经元的神经可塑性。结果雌激素撤退的雌性在高架十字迷宫和旷场测试中焦虑样行为增加，但在蔗糖偏好方面与对照组雌性没有差异。此外，雌激素撤退的女性下丘脑室旁核中的 OT 免疫反应细胞和 OT 信使 RNA 较多，中缝背核中的 OT 受体密度增加。最后，在雌激素撤退期间阻断中缝背核中的 OT 受体可以防止雌激素撤退女性的高度焦虑行为表型。结论 雌激素戒断会诱导下丘脑室旁核和中缝背核的 OT 神经可塑性，从而增加产后的焦虑样行为。 更广泛地说，这些实验表明叙利亚仓鼠是一种新的生物体，可以用来模拟产后雌激素撤退对大脑和焦虑样行为的影响。