Division of Medical Pharmacology, Leiden and Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden University, Leiden, The Netherlands.
PLoS One. 2012;7(6):e39033. doi: 10.1371/journal.pone.0039033. Epub 2012 Jun 22.
Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact) over the course of two weeks. Following novelty exploration, (non-) spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1) the effects of chronic stress persisted beyond the period of the actual rat exposure. (2) Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3) in stressed mice sugar partially "normalized" the impaired performance to the level of controls without sugar. Chronic stress (4) increased behavioral inhibition in response to novelty; (5) induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6) increased the intake of sucrose and water. (7) Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory.
对正性刺激反应降低是抑郁的核心症状，被称为快感缺失。在本研究中，我们使用一小部分读出参数评估慢性应激小鼠模型中的快感缺失表达。与此一致，我们研究了慢性应激是否会影响训练后糖自我给药的促进作用，因为我们之前在未处理的小鼠中观察到了这种作用。雄性 C57BL/6J 小鼠在两周的时间内反复且不可预测地暴露于大鼠（无身体接触）。在新奇性探索、（非）空间学习和记忆过程（有无训练后糖作为强化物）、情绪、奖赏敏感性和皮质酮水平之后，确定了这些参数。我们发现：(1) 慢性应激的影响持续到实际大鼠暴露期之外；(2) 训练后糖作为强化物提高了未处理小鼠的空间表现，而 (3) 在应激小鼠中，糖部分“正常化”了无糖时受损的表现，达到了对照组的水平；(4) 慢性应激增加了对新奇性的行为抑制；(5) 在大鼠应激后的第一周诱导了皮质酮分泌的昼夜节律模式的动态变化；(6) 增加了蔗糖和水的摄入；(7) 慢性应激和空间训练期间消耗的糖促进了几周后蔗糖瓶位置的记忆。总之，我们的慢性应激范式在不同行为水平上诱导了小鼠快感缺失的表达。应激小鼠的行为抑制似乎是持久的。有趣的是，在空间学习的密切背景下消耗的糖部分挽救了应激引起的情绪和认知障碍。这表明奖励可以减轻慢性应激对记忆的部分负面影响。
