Possibility that nitric oxide has a role in the regulation of sleep and consciousness

这个研究项目的负责人和他的同事们发现，N^6-硝基- l -精氨酸甲酯（L-NAME），一种一氧化氮合酶（NOS）的抑制剂，在给大鼠间脑服用后，增加了快速眼动睡眠。另一方面，NOC 12，一种一氧化氮（NO）供体化合物，当被施用于同一区域时，减少了快速眼动睡眠。基于这些和其他结果，我们假设NO在间脑中有调节快速眼动睡眠的作用。可以进一步认为NO参与了意识改变和注意力障碍的病理生理过程。然而，快速眼动睡眠的变化是否归因于间脑NO的定量变化或L-NAME和NOC - 12的其他未知影响尚不清楚。因此，我们在本项目中研究了间脑NO水平是否随昼夜睡眠-觉醒节律而变化，以及L-NAME是否导致间脑NO水平下降。我们对大鼠进行外科手术，植入电极记录脑电图、肌电图和眼电图，并植入两个微透析探针测量间脑NO水平，并在同一区域给予L-NAME。手术完全恢复1周后，将每只大鼠的电极和微透析探针分别连接到各自的设备上。大鼠间脑一氧化氮水平具有昼夜节律性，夜间大鼠活动时一氧化氮水平高，白天大鼠睡眠时一氧化氮水平低。当L-NAME作用于间脑时，NO水平下降。我们的研究结果支持间脑NO参与REM睡眠调节的假设。一氧化氮是否也参与了意识改变和注意力障碍的病理生理，还有待研究。

The head investigator of this research project and his coworkers found that N^6-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), increased REM sleep when administered to the diencephalon of a rat. On the other hand, NOC 12, a nitric oxide (NO) donor compound, decreased REM sleep when administered to the same region. Based on these and other results, we assumed that NO has a role in the diencephalon to regulate REM sleep. It might be further conceived that NO is involved in pathophysiology of altered consciousness and attentional disturbances. However, it is still obscure whether the REM sleep changes were attributed to quantitative changes in NO in the diencephalon or some other unknown effects of L-NAME and NOC 12. Therefore, we investigated in this project whether the level of NO in the diencephalon changes along with a circadian sleep-wake rhythm and whether L-NAME causes a decrease in the level of NO in the diencephalon. We performed surgical operation to rats to implant electrodes to record EEG, EMG and EOG (electrooculogram) and two microdialysis probes to measure the level of NO in the diencephalon and to administer L-NAME to the same region. After full recovery from the surgery for 1 week, electrodes and microdialysis probes of each rat were connected to respective equipments. The level of NO in the rat diencephalon indicated a circadian rhythm, high during night, active period of rats, and low during day when rats spend time sleeping. When L-NAME was administered to the diencephalon, the level of NO showed a decrease. Our results supported the hypothesis that NO in the diencephalon is involved in the regulation of REM sleep. It remains to be studied whether NO is also involved in pathophysiology of altered consciousness and attentional disturbances.