Bogáthy Emese, Papp Noémi, Vas Szilvia, Bagdy György, Tóthfalusi László
Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
MTA-SE, Neuropsychopharmacology and Neurochemistry Research Group, Budapest, Hungary.
Front Pharmacol. 2019 Jul 26;10:831. doi: 10.3389/fphar.2019.00831. eCollection 2019.
(a) To describe the microarchitecture of wakefulness and sleep following administrations of 5- and 10-mg/kg AM-251 in rats. (b) To develop a new statistical method to follow bout-to-bout dynamics. Wistar rats (n = 6) had been equipped with electroencephalography (EEG) and electromyography (EMG) electrodes. Following their recovery and habituation after the surgery, the animals were injected with vehicle and 5- and 10-mg/kg AM-251 intraperitoneally and EEG, EMG, and motor activity were analyzed for the subsequent 3 h. AM-251 induced a dose- and time-dependent increase in the number of bouts in active wake (AW), and it decreased this number in all other vigilance states except in passive wake (PW). In contrast, the bout duration in PW compensatory decreased. The effect of AM-251 on the sleep transition dynamics was monitored with a new tool we call "transition heatmap." The analysis of bout trajectories with transition heatmaps reveals a highly organized pattern. AM-251 selectively influences the frequency of vigilance state transitions, but it has no direct impact on the state lengths. AM-251 markedly changed the state transition dynamics, which was visualized with the help of state transition heatmaps.
(a) 描述大鼠腹腔注射5毫克/千克和10毫克/千克AM - 251后清醒和睡眠的微观结构。(b) 开发一种新的统计方法来跟踪逐段动态变化。将Wistar大鼠（n = 6）植入脑电图（EEG）和肌电图（EMG）电极。在手术后恢复和适应环境后，给动物腹腔注射赋形剂、5毫克/千克和10毫克/千克的AM - 251，并在随后3小时内分析EEG、EMG和运动活动。AM - 251引起主动清醒（AW）时段数量呈剂量和时间依赖性增加，并且除被动清醒（PW）外，它使所有其他警觉状态下的时段数量减少。相比之下，PW中的时段持续时间代偿性缩短。用我们称为“转换热图”的新工具监测AM - 251对睡眠转换动态的影响。用转换热图分析时段轨迹揭示了一种高度有组织的模式。AM - 251选择性地影响警觉状态转换的频率，但对状态时长没有直接影响。AM - 251显著改变了状态转换动态，这借助状态转换热图得以直观呈现。
