Mekiri Maryam, Gardier Alain M, David Denis J, Guilloux Jean-Philippe
Faculté de Pharmacie, Centre d'étude des supports de publicité, Unité Mixte de Recherche Scientifique-1178, Institut national de la santé et de la recherche médicale, Université Paris-Saclay, Université Paris-Sud.
Exp Clin Psychopharmacol. 2017 Apr;25(2):94-104. doi: 10.1037/pha0000112. Epub 2017 Mar 13.
Understanding the pathophysiology of affective disorders and their treatment relies on the availability of experimental models that mimic aspects of the disease. Most of the studies on depressive disorders are conducted with male rodents, mostly because including females in protocols is more difficult. Indeed, there is a complex series of changes in the brain of females due to the estrous cycle, adding an important variability factor to the disease. However, twice as many women as men have a lifetime diagnosis of major depressive disorder (MDD), so we need to develop reliable female models of depression to improve our understanding of this disease. Here, we describe the effects of chronic corticosterone administration (CORT) on female mice, a procedure known to enhance behavioral emotionality in male mice. A dose-response study showed that 4 weeks of CORT exposure at 35 μg/ml in the drinking water enhanced the emotionality score of female mice, but with a very small size effect. Tests of longer treatment duration failed to potentiate the behavioral effects of CORT. As some steps of adult hippocampal neurogenesis are known to be sensitive to chronic CORT exposure, cell proliferation and survival, as well as neuronal maturation in the dentate gyrus of the hippocampus, analyses revealed no effect of chronic CORT exposure in female mice. Overall, this study showed that female C57BL6 mice are insensitive to chronic CORT as a way to model anxio-depressive-like behavior. (PsycINFO Database Record
了解情感障碍的病理生理学及其治疗方法依赖于能够模拟疾病各个方面的实验模型。大多数关于抑郁症的研究都是用雄性啮齿动物进行的，主要是因为在实验方案中纳入雌性动物更加困难。实际上，由于发情周期，雌性动物大脑会发生一系列复杂的变化，这给疾病增加了一个重要的可变因素。然而，终生被诊断为重度抑郁症（MDD）的女性人数是男性的两倍，所以我们需要开发可靠的雌性抑郁症模型，以增进我们对这种疾病的了解。在此，我们描述了慢性给予皮质酮（CORT）对雌性小鼠的影响，这一过程已知会增强雄性小鼠的行为情绪反应。一项剂量反应研究表明，在饮用水中以35μg/ml的剂量给予CORT 4周，可提高雌性小鼠的情绪评分，但效应量非常小。更长治疗时长的测试未能增强CORT的行为效应。由于已知成年海马神经发生的某些步骤对慢性CORT暴露敏感，对海马齿状回中的细胞增殖与存活以及神经元成熟情况进行分析后发现，慢性CORT暴露对雌性小鼠没有影响。总体而言，本研究表明，雌性C57BL6小鼠对慢性CORT不敏感，无法以此作为模拟焦虑抑郁样行为的方法。（《心理学文摘数据库记录》
