Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice.,Translational Psychiatry

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Chronic corticosterone administration induces negative valence and impairs positive valence behaviors in mice.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-12-10 , DOI: 10.1038/s41398-019-0674-4
Andrew Dieterich _{1,

2} , Prachi Srivastava ₂ , Aitesam Sharif ₂ , Karina Stech ₂ , Joseph Floeder ₂ , Samantha E Yohn ₃ , Benjamin A Samuels _{1,

2}

Affiliation

Behavioral approaches utilizing rodents to study mood disorders have focused primarily on negative valence behaviors associated with potential threat (anxiety-related behaviors). However, for disorders such as depression, positive valence behaviors that assess reward processing may be more translationally valid and predictive of antidepressant treatment outcome. Chronic corticosterone (CORT) administration is a well-validated pharmacological stressor that increases avoidance in negative valence behaviors associated with anxiety1-4. However, whether chronic stress paradigms such as CORT administration also lead to deficits in positive valence behaviors remains unclear. We treated male C57BL/6J mice with chronic CORT and assessed both negative and positive valence behaviors. We found that CORT induced avoidance in the open field and NSF. Interestingly, CORT also impaired instrumental acquisition, reduced sensitivity to a devalued outcome, reduced breakpoint in progressive ratio, and impaired performance in probabilistic reversal learning. Taken together, these results demonstrate that chronic CORT administration at the same dosage both induces avoidance in negative valence behaviors associated with anxiety and impairs positive valence behaviors associated with reward processing. These data suggest that CORT administration is a useful experimental system for preclinical approaches to studying stress-induced mood disorders.

中文翻译：

长期给予皮质酮会诱导负价并损害小鼠的正价行为。

利用啮齿动物研究情绪障碍的行为方法主要集中于与潜在威胁相关的负价行为（焦虑相关行为）。然而，对于抑郁症等疾病，评估奖励处理的正效价行为可能更有效，并且可以预测抗抑郁治疗的结果。慢性皮质酮 (CORT) 给药是一种经过充分验证的药理应激源，可增加对与焦虑相关的负价行为的避免1-4。然而，诸如 CORT 管理等慢性应激范式是否也会导致正价行为的缺陷仍不清楚。我们用慢性 CORT 治疗雄性 C57BL/6J 小鼠，并评估负价和正价行为。我们发现 CORT 在旷场和 NSF 中诱导回避。有趣的是，CORT 还会损害工具性习得，降低对贬值结果的敏感性，减少渐进比率的断点，并损害概率逆转学习的表现。总而言之，这些结果表明，长期给予相同剂量的 CORT 既会诱导与焦虑相关的负价行为的回避，又会损害与奖励处理相关的正价行为。这些数据表明，CORT 给药是一种有用的实验系统，可用于研究压力引起的情绪障碍的临床前方法。

更新日期：2019-12-11

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