Rachman I M, Unnerstall J R, Pfaff D W, Cohen R S
Department of Anatomy and Cell Biology, University of Illinois, 808 South Wood Street, Chicago, IL 60612, USA.
Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13941-6. doi: 10.1073/pnas.95.23.13941.
Estrogen has been implicated in brain functions related to affective state, including hormone-related affective disorders in women. Although some reports suggest that estrogen appears to decrease vulnerability to affective disorders in certain cases, the mechanisms involved are unknown. We used the forced swim test (FST), a paradigm used to test the efficacy of antidepressants, and addressed the hypotheses that estrogen alters behavior of ovariectomized rats in the FST and the FST-induced expression of c-fos, a marker for neuronal activity, in the rat forebrain. The behaviors displayed included struggling, swimming, and immobility. One hour after the beginning of the test on day 2, the animals were perfused, and the brains were processed for c-fos immunocytochemistry. On day 1, the estradiol benzoate-treated animals spent significantly less time struggling and virtually no time in immobility and spent most of the time swimming. Control rats spent significantly more time struggling or being immobile during a comparable period. On day 2, similar behavioral patterns with still more pronounced differences were observed between estradiol benzoate and ovariectomized control groups in struggling, immobility, and swimming. Analysis of the mean number of c-fos immunoreactive cell nuclei showed a significant reduction in the estradiol benzoate versus control groups in areas of the forebrain relating to sensory, contextual, and integrative processing. Our results suggest that estrogen-induced neurochemical changes in forebrain neurons may translate into an altered behavioral output in the affective domain.
雌激素与包括女性激素相关情感障碍在内的、与情感状态有关的脑功能存在关联。尽管一些报告表明，在某些情况下雌激素似乎能降低患情感障碍的易感性，但其涉及的机制尚不清楚。我们使用了强迫游泳试验（FST），这是一种用于测试抗抑郁药疗效的范式，并探讨了雌激素会改变去卵巢大鼠在FST中的行为以及FST诱导的大鼠前脑神经元活动标记物c-fos表达的假设。所表现出的行为包括挣扎、游泳和不动。在第2天试验开始1小时后，对动物进行灌注，并对大脑进行c-fos免疫细胞化学处理。在第1天，接受苯甲酸雌二醇治疗的动物挣扎时间显著减少，几乎没有不动的时间，大部分时间用于游泳。在同一时期，对照大鼠挣扎或不动的时间显著更多。在第2天，苯甲酸雌二醇组和去卵巢对照组在挣扎、不动和游泳方面观察到类似的行为模式，且差异更为明显。对c-fos免疫反应性细胞核平均数量的分析表明，在前脑与感觉、情境和整合处理相关的区域，苯甲酸雌二醇组与对照组相比显著减少。我们的结果表明，雌激素诱导的前脑神经元神经化学变化可能转化为情感领域行为输出的改变。
