Garrity Abigail G, Botta Simhadri, Lazar Stephanie B, Swor Erin, Vanini Giancarlo, Baghdoyan Helen A, Lydic Ralph
Neuroscience Program, University of Michigan, Ann Arbor, MI.
Department of Anesthesiology, University of Michigan, Ann Arbor, MI.
Sleep. 2015 Jan 1;38(1):73-84. doi: 10.5665/sleep.4328.
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.
This study used between-groups and within-groups designs.
University of Michigan.
Adult male Sprague Dawley rats (n = 40).
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.
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 level. 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.
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.
右美托咪定在临床上用于诱导被描述为与非快速眼动（NREM）睡眠相似的镇静状态。更好地理解NREM睡眠和右美托咪定诱导的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。本研究检验了右美托咪定诱导的镇静与睡眠相似的假设。
本研究采用组间和组内设计。
密歇根大学。
成年雄性斯普拉格-道利大鼠（n = 40）。
自变量为右美托咪定以及生理盐水或林格氏液（对照）的给药。因变量包括清醒、睡眠和镇静状态下所花费的时间、脑电图（EEG）功率、无名质（SI）中的腺苷水平以及睡眠相关前脑区域中pCREB和c-Fos的激活情况。
右美托咪定显著减少了清醒时间（-49%），增加了镇静持续时间（1995%），增加了EEGδ波功率（546%），并在16小时内消除了睡眠的快速眼动（REM）阶段。镇静后NREM和REM睡眠出现反弹增加。全身给予右美托咪定显著降低了（-39%）SI腺苷水平。将右美托咪定通过透析注入SI并未降低腺苷水平。全身给予右美托咪定未改变下丘脑水平对角带、腹外侧、正中及内侧视前区中c-Fos或pCREB的表达。
右美托咪定显著改变了正常睡眠表型，且右美托咪定诱导的状态无法补偿睡眠需求。因此，在斯普拉格-道利大鼠中，右美托咪定诱导的镇静具有行为、电图和免疫组化表型，这些表型与睡眠期间获得的类似测量结果明显不同。
