Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL 32306, USA.
Horm Behav. 2011 Mar;59(3):331-7. doi: 10.1016/j.yhbeh.2010.09.005. Epub 2010 Sep 21.
Major depression is a growing problem worldwide with variation in symptoms and response to treatment. Individual differences in response to stress may contribute to such observed individual variation in behavior and pathology. Therefore, we investigated depressive-like behavior following exposure to repeated social defeat in a rat model of individual differences in response to novelty. Rats are known to exhibit either high locomotor activity and sustained exploration (high responders, HR) or low activity with minimal exploration (low responders, LR) in a novel environment. We measured anhedonia using the sucrose preference test in HR and LR rats following exposure to social defeat stress or in basal, non-defeated conditions. We then compared histone acetylation in the hippocampus in HR and LR defeat and non-defeated rats and measured mRNA levels of histone deacetylases (HDAC) 3, 4, 5, and Creb binding protein (CBP). We found that basally, HR rats consumed more sucrose solution than LR rats, but reduced consumption after exposure to defeat. LR rats' preference was unaffected by social defeat. We found that HR rats had higher levels of histone acetylation on H3K14 and H2B than LR rats in non-stress conditions. Following defeat, this acetylation pattern changed differentially, with HR rats decreasing acetylation of H3K14 and H2B and LR's increasing acetylation of H3K14. Acetylation on histone H4 decreased following defeat with no individual variation. Basal differences in CBP expression levels may underlie the observed acetylation pattern; however we found no significant effects of defeat in levels of HDACs 3, 4, 5 in the hippocampus.
重度抑郁症是全球范围内日益严重的问题，其症状和治疗反应存在差异。个体对压力的反应差异可能导致行为和病理方面观察到的个体差异。因此，我们在对新奇反应存在个体差异的大鼠模型中，研究了反复社会挫败后出现的抑郁样行为。众所周知，大鼠在新环境中表现出高运动活性和持续探索（高反应者，HR）或低活性和最小探索（低反应者，LR）。我们在 HR 和 LR 大鼠暴露于社会挫败应激或在基础、未受挫条件下，使用蔗糖偏好测试测量快感缺失。然后，我们比较了 HR 和 LR 挫败和未挫败大鼠海马体中的组蛋白乙酰化，并测量了组蛋白去乙酰化酶（HDAC）3、4、5 和 Creb 结合蛋白（CBP）的 mRNA 水平。我们发现，基础状态下，HR 大鼠比 LR 大鼠消耗更多的蔗糖溶液，但暴露于挫败后消耗减少。LR 大鼠的偏好不受社会挫败的影响。我们发现，HR 大鼠在非应激条件下，H3K14 和 H2B 的组蛋白乙酰化水平高于 LR 大鼠。在挫败后，这种乙酰化模式发生了不同的变化，HR 大鼠 H3K14 和 H2B 的乙酰化减少，LR 大鼠的 H3K14 乙酰化增加。在没有个体差异的情况下，挫败后组蛋白 H4 的乙酰化减少。基础 CBP 表达水平的差异可能是观察到的乙酰化模式的基础；然而，我们没有发现海马体中 HDACs 3、4、5 水平在挫败后有显著影响。
