Genetic deletion of MT1 melatonin receptors alters spontaneous behavioral rhythms in male and female C57BL/6 mice.

Genetic deletion of MT1 melatonin receptors alters spontaneous behavioral rhythms in male and female C57BL/6 mice.
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DOI:
10.1016/j.yhbeh.2014.08.012
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发表时间:
2014-09
影响因子:
3.5
通讯作者:
Dubocovich ML
Dubocovich ML
中科院分区:
医学3区
文献类型:
--
作者:
Adamah-Biassi EB;Hudson RL;Dubocovich ML

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行为在24小时的光/暗周期内变化,这些时间模式部分反映了昼夜神经回路和激素(如褪黑激素)的调节。本研究的目的是通过比较雄性和雌性C57野生型(WT)小鼠与MT 1受体基因缺失(MT 1 KO)的C57小鼠,研究MT 1褪黑激素受体是否参与行为调节。使用HomeCageScan系统连续多日在家庭笼中记录了15种不同自发行为的综合阵列。评估的行为是活动样(即下来、悬挂、跳跃、行走)、探索样(即挖掘、梳理、竖起、嗅闻、伸展)、休息样(即清醒、保持低姿势、休息、抽搐)和摄入样(即饮水、进食)。表型阵列和时间分布分析显示WT和MT 1 KO小鼠之间存在不同的行为节律。雄虫的这种节律每天都是一致的,而雌虫则随发情周期而变化。我们还研究了MT 1受体在抑郁和焦虑样行为中的作用。MT 1受体的基因缺失增加了强迫游泳试验中的不动时间,并减少了雄性和雌性C57小鼠在大理石埋藏试验中埋藏的大理石数量。我们的结论是,MT 1褪黑激素受体参与神经通路调节昼夜节律的自发行为在homecage以及通路调节抑郁和抗焦虑样行为。
Behaviors vary over the 24 hr. light/dark cycle and these temporal patterns reflect in part modulation by circadian neural circuits and hormones, such as melatonin. The goal of this study was to investigate if MT1 melatonin receptors are involved in behavioral regulation by comparing male and female C57 wild type (WT) mice with C57 mice that had a genetic deletion of the MT1 receptor (MT1KO). A comprehensive array of fifteen distinct spontaneous behaviors was recorded continuously in the homecage over multiple days using the HomeCageScan system. Behaviors assessed were activity-like (i.e. come down, hang, jump, walk), exploration-like (i.e. dig, groom, rear up, sniff, stretch), resting-like (i.e. awake, remain low, rest, twitch) and ingestion-like (i.e. drink, eat). Phenotypic array and temporal distribution analysis revealed distinct behavioral rhythms that differed between WT and MT1KO mice. The rhythms were consistent from day to day in males and varied with the estrous cycle in females. We also studied the role of MT1 receptors on depressive and anxiety-like behaviors. Genetic deletion of MT1 receptors increased immobility time in the forced swim test and decreased the number of marbles buried in the marble burying test in both male and female C57 mice. We conclude that MT1 melatonin receptors are involved in neural pathways modulating diurnal rhythms of spontaneous behavior in the homecage as well as pathways regulating depressive and anxiolytic-like behaviors.