Dexmedetomidine-Induced Sedation Does Not Mimic the Neurobehavioral Phenotypes of Sleep in Sprague Dawley Rat
Dexmedetomidine-Induced Sedation Does Not Mimic the Neurobehavioral Phenotypes of Sleep in Sprague Dawley Rat
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DOI：
10.5665/sleep.4328
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发表时间：
2015-01-01
期刊：
影响因子：
5.6
通讯作者：
Lydic, Ralph
中科院分区：
文献类型：
--
作者：
Garrity, Abigail G.;Botta, Simhadri;Lydic, Ralph
研究目的：右美托咪定在临床上用于诱导与非快速眼动（NREM）睡眠相似的镇静状态。更好地了解NREM睡眠和右美托咪定诱导镇静之间的异同对于阐明这两种状态之间的关系至关重要。本研究验证了右美托咪定诱导的镇静与睡眠同源的假设。设计：本研究采用组间和组内设计。单位：密歇根大学。实验对象：成年雄性Sprague Dawley大鼠（n = 40）。干预措施：自变量为右美托咪定和生理盐水或林格液（对照）的使用。相关变量包括处于清醒、睡眠和镇静状态的时间、脑电图（EEG）功率、无名物质（SI）中的腺苷水平以及与睡眠相关的前脑区域中pCREB和c-Fos的激活。测量和结果：右美托咪定显著减少清醒时间（-49%），增加镇静持续时间（1995%），增加EEG δ功率（546%），并消除快速眼动（REM）睡眠期16小时。镇静后，非快速眼动和快速眼动睡眠反弹增加。系统给予右美托咪定显著降低（-39%）SI腺苷水平。透析输送右美托咪定到SI没有降低腺苷水平。右美托咪定全身给药没有改变水平对角带、下丘脑腹外侧、正中和内侧视前区c-Fos或pCREB的表达。结论：右美托咪定显著改变了正常睡眠表型，右美托咪定诱导的状态不能补偿睡眠需求。因此，在Sprague Dawley大鼠中，右美托咪定诱导的镇静表现为行为、电图和免疫组织化学表型，与睡眠时获得的类似测量结果明显不同。
Study Objectives: Dexmedetomidine is used clinically to induce states of sedation that have been described as homologous to nonrapid eye movement (NREM) sleep. A better understanding of the similarities and differences between NREM sleep and dexmedetomidine-induced sedation is essential for efforts to clarify the relationship between these two states. This study tested the hypothesis that dexmedetomidine-induced sedation is homologous to sleep.Design: This study used between-groups and within-groups designs.Setting: University of Michigan.Participants: Adult male Sprague Dawley rats (n = 40).Interventions: Independent variables were administration of dexmedetomidine and saline or Ringer's solution (control). Dependent variables included time spent in states of wakefulness, sleep, and sedation, electroencephalographic (EEG) power, adenosine levels in the substantia innominata (SI), and activation of pCREB and c-Fos in sleep related forebrain regions.Measurements and Results: Dexmedetomidine significantly decreased time spent in wakefulness (-49%), increased duration of sedation (1995%), increased EEG delta power (546%), and eliminated the rapid eye movement (REM) phase of sleep for 16 h. Sedation was followed by a rebound increase in NREM and REM sleep. Systemically administered dexmedetomidine significantly decreased (-39%) SI adenosine levels. Dialysis delivery of dexmedetomidine into SI did not decrease adenosine levels. Systemic delivery of dexmedetomidine did not alter c-Fos or pCREB expression in the horizontal diagonal band, or ventrolateral, median, and medial preoptic areas of the hypothalamus.Conclusions: Dexmedetomidine significantly altered normal sleep phenotypes, and the dexmedetomidine-induced state did not compensate for sleep need. Thus, in the Sprague Dawley rat, dexmedetomidine-induced sedation is characterized by behavioral, electrographic, and immunohistochemical phenotypes that are distinctly different from similar measures obtained during sleep.