Prenatal alcohol exposure and chronic mild stress differentially alter depressive- and anxiety-like behaviors in male and female offspring.
Prenatal alcohol exposure and chronic mild stress differentially alter depressive- and anxiety-like behaviors in male and female offspring.
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DOI：
10.1111/j.1530-0277.2009.01132.x
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发表时间：
2010-04
期刊：
影响因子：
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通讯作者：
Weinberg J
中科院分区：
文献类型：
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作者：
Hellemans KG;Verma P;Yoon E;Yu WK;Young AH;Weinberg J
胎儿酒精谱系障碍（FASD）与许多神经行为改变以及许多领域的残疾有关，包括抑郁症和焦虑症的高发病率。产前酒精暴露（PAE）也会改变下丘脑-垂体-肾上腺（HPA）功能，导致成年后对应激源的反应性增加和HPA失调。有趣的是，数据表明，预先存在的HPA异常可能是某些形式的抑郁症的主要促成因素，特别是当一个人在以后的生活中暴露于压力源时。我们测试了这一假设，即在成年期暴露于压力源可能会揭示PAE动物对抑郁和焦虑样行为的脆弱性增加。在成年期对产前酒精（PAE）、配对喂养（PF）和随意喂养对照（C）处理组的雄性和雌性后代进行检测。将动物暴露于连续10天的慢性轻度应激（CMS），并在一组对抑郁和/或焦虑样行为差异敏感的经过充分验证的任务中进行评估。我们在这里报告说，PAE和CMS在成年期的组合增加抑郁和焦虑样行为的性二态性的方式。PAE男性表现出受损的享乐反应（蔗糖对比试验），运动多动（开放领域），并在从属和非从属的社会行为（社会互动测试）相比，控制男性的改变。相比之下，PAE和，在较小程度上，PF，女性在强迫游泳测试中表现出更高水平的“行为绝望”，PAE女性在社会互动测试的最后5分钟与对照女性相比，表现出改变的行为。这些数据支持压力可能是FASD人群中报告的精神病理学的介导或促成因素的可能性。
Fetal Alcohol Spectrum Disorder (FASD) is associated with numerous neuro behavioral alterations, as well as disabilities in a number of domains, including a high incidence of depression and anxiety disorders. Prenatal alcohol exposure (PAE) also alters hypothalamic-pituitary-adrenal (HPA) function, resulting in increased responsiveness to stressors and HPA dysregulation in adulthood. Interestingly, data suggest that pre-existing HPA abnormalities may be a major contributory factor to some forms of depression, particularly when an individual is exposed to stressors later in life. We tested the hypothesis that exposure to stressors in adulthood may unmask an increased vulnerability to depressive- and anxiety-like behaviors in PAE animals. Male and female offspring from prenatal alcohol (PAE), pair-fed (PF), and ad libitumfed control (C) treatment groups were tested in adulthood. Animals were exposed to 10 consecutive days of chronic mild stress (CMS), and assessed in a battery of well-validated tasks sensitive to differences in depressive- and / or anxiety-like behaviors. We report here that the combination of PAE and CMS in adulthood increases depressive- and anxiety-like behaviors in a sexually dimorphic manner. PAE males showed impaired hedonic responsivity (sucrose contrast test), locomotor hyperactivity (open field), and alterations in affiliative and nonaffiliative social behaviors (social interaction test) compared to control males. By contrast, PAE and, to a lesser extent, PF, females showed greater levels of “behavioral despair” in the forced swim test, and PAE females showed altered behavior in the final 5 minutes of the social interaction test compared to control females. These data support the possibility that stress may be a mediating or contributing factor in the psychopathologies reported in FASD populations.