Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.
Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior.
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DOI：
10.3109/07853890.2015.1122216
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发表时间：
2016
影响因子：
4.4
通讯作者：
Pollak DD
中科院分区：
文献类型：
--
作者：
Schaufler J;Ronovsky M;Savalli G;Cabatic M;Sartori SB;Singewald N;Pollak DD
简介 昼夜节律紊乱是情绪和焦虑障碍的关键症状。选择性血清素再摄取抑制剂（SSRI）——常用的抗抑郁药物——也能调节昼夜节律。然而，它们恢复抑郁症昼夜节律紊乱的潜力仍有待研究。 材料和方法 使用选择性培育的高度焦虑相关和共分离抑郁样行为 (HAB) 小鼠和正常焦虑/抑郁行为小鼠 (NAB) 来检查 SSRI 氟西汀对行为和分子水平上基于遗传的抑郁相关昼夜节律紊乱的影响。 结果与 NAB 小鼠相比，氟西汀处理的 HAB 小鼠的昼夜节律周期长度增加，而活动次数和光诱导的夹带次数相当。先前报道未治疗的 HAB 小鼠海马 Cry2 表达失衡，但未观察到海马 Cry2 表达存在差异，而氟西汀治疗的 HAB 小鼠中 Per2 和 Per3 mRNA 水平较高。 讨论目前的研究结果提供了证据，表明氟西汀治疗可以使高特质焦虑和抑郁的遗传小鼠模型中扰乱的昼夜节律运动活动和时钟基因表达正常化。提出了介导氟西汀抗抑郁反应的分子机制与基于遗传的情绪和焦虑症的昼夜节律的内源性调节之间的相互作用。
Introduction Disturbances of circadian rhythms are a key symptom of mood and anxiety disorders. Selective serotonin reuptake inhibitors (SSRIs) - commonly used antidepressant drugs – also modulate aspects of circadian rhythmicity. However, their potential to restore circadian disturbances in depression remains to be investigated. Materials and methods The effects of the SSRI fluoxetine on genetically based, depression-related circadian disruptions at the behavioral and molecular level were examined using mice selectively bred for high anxiety-related and co-segregating depression-like behavior (HAB) and normal anxiety/depression behavior mice (NAB). Results The length of the circadian period was increased in fluoxetine-treated HAB as compared to NAB mice while the number of activity bouts and light-induced entrainment were comparable. No difference in hippocampal Cry2 expression, previously reported to be dysbalanced in untreated HAB mice, was observed, while Per2 and Per3 mRNA levels were higher in HAB mice under fluoxetine treatment. Discussion The present findings provide evidence that fluoxetine treatment normalizes disrupted circadian locomotor activity and clock gene expression in a genetic mouse model of high trait anxiety and depression. An interaction between the molecular mechanisms mediating the antidepressant response to fluoxetine and the endogenous regulation of circadian rhythms in genetically based mood and anxiety disorders is proposed.