Physiology Department, Michigan State University, East Lansing, Michigan.
Department of Psychology, Haverford College, Haverford, Pennsylvania.
Biol Psychiatry. 2021 May 1;89(9):929-938. doi: 10.1016/j.biopsych.2020.11.016. Epub 2020 Nov 24.
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.
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 Ovariectomized females were given daily injections to approximate hormone levels during gestation and then withdrawn from estrogen to simulate postpartum estrogen withdrawal.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.
Estrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus maze and open field tests but did not differ from control females in sucrose preference. Furthermore, estrogen-withdrawn females had more OT-immunoreactive cells and OT messenger RNA in the paraventricular nucleus of the hypothalamus and an increase in OT receptor density in the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in the dorsal raphe nucleus during estrogen withdrawal prevented the high-anxiety behavioral phenotype in estrogen-withdrawn females.
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.
雌激素在怀孕期间会急剧增加，但在分娩时迅速降至孕前水平，并在产后期间持续受到抑制。临床和啮齿动物研究表明，这种产后雌激素下降导致雌激素撤退状态，与情感、情绪和行为的变化有关。雌激素撤退如何影响催产素（OT）神经回路尚未得到研究。
我们使用激素模拟的假孕，然后在叙利亚仓鼠中进行雌激素撤退，这在该物种中尚属首次。卵巢切除的雌性动物每天接受注射，以模拟妊娠期间的激素水平，然后停止雌激素注射以模拟产后雌激素撤退。在雌激素撤退期间，这些仓鼠接受焦虑和快感缺失行为测试。测量下丘脑室旁核中产生 OT 的神经元及其传出靶标的神经可塑性。
雌激素撤退的雌性在高架十字迷宫和旷场测试中表现出更多的焦虑样行为，但在蔗糖偏好方面与对照组雌性没有差异。此外，雌激素撤退的雌性在下丘脑室旁核中具有更多的 OT-免疫反应细胞和 OT 信使 RNA，并且在中缝背核中 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 受体可防止雌激素撤退的雌性出现高焦虑行为表型。
雌激素撤退在下丘脑室旁核和中缝背核中诱导 OT 神经可塑性，以增加产后期间的焦虑样行为。更广泛地说，这些实验表明叙利亚仓鼠是一种新的生物体，可用于模拟产后雌激素撤退对大脑和焦虑样行为的影响。
