Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Physiol Behav. 2011 May 3;103(2):210-6. doi: 10.1016/j.physbeh.2011.02.001. Epub 2011 Feb 12.
The onset of major depressive disorder is likely precipitated by a combination of heredity and life stress. The present study tested the hypothesis that rats selectively bred on a trait related to emotional reactivity would show differential susceptibility or resilience to the development of depression-like signs in response to chronic mild variable intermittent stress (CMS).
Male Sprague-Dawley rats that were bred based on the trait of either high or low locomotor activity in response to a novel environment were exposed to 4 weeks of CMS or control conditions. Changes in hedonic behavior were assessed using weekly sucrose preference tests and anxiety-like behavior was evaluated using the novelty-suppressed feeding test.
During 4 weeks of CMS, bred low responder (bLR) rats became anhedonic at a faster rate and to a larger degree than bred high responder (bHR) rats, based on weekly sucrose preference tests. Measures of anxiety-like behavior in the novelty-suppressed feeding test were also significantly increased in the CMS-exposed bLR rats, though no differences were observed between CMS-exposed bHR rats and their unstressed controls.
These findings present further evidence that increased emotional reactivity is an important factor in stress susceptibility and the etiology of mood disorders, and that bHR and bLR rats provide a model of resistance or vulnerability to stress-induced depression. Furthermore, exposing bHR and bLR rats to CMS provides an excellent way to study the interaction of genetic and environmental factors in the development of depression-like behavior.
重度抑郁症的发病可能是遗传和生活压力共同作用的结果。本研究检验了这样一个假设，即具有情绪反应相关特征的选择性繁殖大鼠，在应对慢性轻度可变间歇应激（CMS）时，会表现出对抑郁样症状发展的不同易感性或弹性。
根据对新环境的反应表现出高或低运动活性的特征，对雄性 Sprague-Dawley 大鼠进行选择性繁殖，然后将其暴露于 4 周的 CMS 或对照条件下。使用每周蔗糖偏好测试评估享乐行为的变化，使用新奇抑制进食测试评估焦虑样行为。
在 4 周的 CMS 期间，根据每周蔗糖偏好测试，与 bred high responder（bHR）大鼠相比，bred low responder（bLR）大鼠更快且更大程度地出现快感缺失。在新奇抑制进食测试中，CMS 暴露的 bLR 大鼠的焦虑样行为测量值也显著增加，尽管 CMS 暴露的 bHR 大鼠与其未受应激的对照组之间没有差异。
这些发现进一步证明了情绪反应增强是应激易感性和情绪障碍病因的一个重要因素，并且 bHR 和 bLR 大鼠提供了对应激诱导的抑郁易感性或弹性的模型。此外，将 bHR 和 bLR 大鼠暴露于 CMS 为研究抑郁样行为发展中遗传和环境因素的相互作用提供了一种极好的方法。
