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昼夜节律运动参数的个体差异与焦虑样和抑郁样行为相关。

Individual differences in circadian locomotor parameters correlate with anxiety- and depression-like behavior.

作者信息

Anyan Jeffrey, Verwey Michael, Amir Shimon

机构信息

Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada.

出版信息

PLoS One. 2017 Aug 1;12(8):e0181375. doi: 10.1371/journal.pone.0181375. eCollection 2017.

Abstract

Disrupted circadian rhythms are a core feature of mood and anxiety disorders. Circadian rhythms are coordinated by a light-entrainable master clock located in the suprachiasmatic nucleus. Animal models of mood and anxiety disorders often exhibit blunted rhythms in locomotor activity and clock gene expression. Interestingly, the changes in circadian rhythms correlate with mood-related behaviours. Although animal models of depression and anxiety exhibit aberrant circadian rhythms in physiology and behavior, it is possible that the methodology being used to induce the behavioral phenotype (e.g., brain lesions, chronic stress, global gene deletion) affect behavior independently of circadian system. This study investigates the relationship between individual differences in circadian locomotor parameters and mood-related behaviors in healthy rats. The circadian phenotype of male Lewis rats was characterized by analyzing wheel running behavior under standard 12h:12h LD conditions, constant dark, constant light, and rate of re-entrainment to a phase advance. Rats were then tested on a battery of behavioral tests: activity box, restricted feeding, elevated plus maze, forced swim test, and fear conditioning. Under 12h:12h LD conditions, percent of daily activity in the light phase and variability in activity onset were associated with longer latency to immobility in the forced swim test. Variability in onset also correlated positively with anxiety-like behavior in the elevated plus maze. Rate of re-entrainment correlated positively with measures of anxiety in the activity box and elevated plus maze. Lastly, we found that free running period under constant dark was associated with anxiety-like behaviors in the activity box and elevated plus maze. Our results provide a previously uncharacterized relationship between circadian locomotor parameters and mood-related behaviors in healthy rats and provide a basis for future examination into circadian clock functioning and mood.

摘要

昼夜节律紊乱是情绪和焦虑障碍的核心特征。昼夜节律由位于视交叉上核的可被光线调节的主时钟协调。情绪和焦虑障碍的动物模型通常在运动活动和时钟基因表达方面表现出节律减弱。有趣的是,昼夜节律的变化与情绪相关行为相关。尽管抑郁和焦虑的动物模型在生理和行为上表现出异常的昼夜节律,但用于诱导行为表型的方法(例如,脑损伤、慢性应激、全局基因缺失)可能独立于昼夜节律系统影响行为。本研究调查了健康大鼠昼夜运动参数的个体差异与情绪相关行为之间的关系。通过分析雄性Lewis大鼠在标准12小时:12小时明暗周期条件、持续黑暗、持续光照以及重新适应相位提前的速率下的转轮行为,来表征其昼夜表型。然后对大鼠进行一系列行为测试:活动箱测试、限时进食、高架十字迷宫、强迫游泳测试和恐惧条件反射。在12小时:12小时明暗周期条件下,光照期的每日活动百分比和活动开始的变异性与强迫游泳测试中不动的延迟时间较长有关。开始的变异性也与高架十字迷宫中的焦虑样行为呈正相关。重新适应的速率与活动箱和高架十字迷宫中的焦虑测量呈正相关。最后,我们发现持续黑暗下的自由运行周期与活动箱和高架十字迷宫中的焦虑样行为有关。我们的结果揭示了健康大鼠昼夜运动参数与情绪相关行为之间以前未被描述的关系,并为未来研究昼夜节律时钟功能和情绪提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3d0/5538649/7c581969abb1/pone.0181375.g001.jpg

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