Nitric oxide and sleep in the rat: A puzzling relationship
Nitric oxide and sleep in the rat: A puzzling relationship
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DOI：
10.1016/s0306-4522(99)00031-7
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发表时间：
1999-01-01
期刊：
影响因子：
3.3
通讯作者：
Cespuglio, R
中科院分区：
文献类型：
--
作者：
Burlet, S;Leger, L;Cespuglio, R
迄今为止，只有少数研究表明，一氧化氮可能在调节睡眠-觉醒周期中发挥作用。然而，报道的数据是有争议的，一氧化氮在睡眠-觉醒周期调节中的作用仍然不确定。在本报告中，我们研究了两种不同的一氧化氮合酶抑制剂对睡眠量的影响：N-硝基-L-精氨酸甲酯，一种非选择性一氧化氮合酶抑制剂，和7-硝基-吲唑，神经元型一氧化氮合酶的特异性抑制剂。上述化合物通过两种途径给药，即腹膜内给药或中缝背核局部给药，中缝背核是一种参与睡眠调节的结构。为了评价它们抑制大鼠脑中一氧化氮合成的效率，首先将它们腹膜内给予一组动物，并通过伏安测量法测定一氧化氮的皮质释放。N-硝基-L-精氨酸甲酯（100 mg/kg，i.p）不影响皮层一氧化氮的释放，但增加慢波睡眠和异相睡眠持续时间。相反，7-硝基-吲唑（40 mg/kg，i. p.）显著降低皮层一氧化氮释放（-25%）和异相睡眠持续时间。此外，在中缝背核的一氧化氮能细胞区微量注射100 ng/0.20 μ l的N-硝基-L-精氨酸甲酯或7-硝基-吲唑后，获得了异相睡眠持续时间的减少（分别为-32.8%和-25.3%）。所获得的结果支持一氧化氮在睡眠调节模式中存在双重性，即对中缝背核的一氧化氮能神经元的外周抑制作用和中枢促进作用。(C)1999年IBRO。出版社：Elsevier Science Ltd
To date, only a few studies indicate that nitric oxide may play a role in the regulation of the sleep-wake cycle. However, data reported are controversial and the pan played by nitric oxide in sleep-wake cycle regulation still remains uncertain. In the present report, we studied the effects on sleep amounts of two different nitric oxide synthase inhibitors: N-nitro-L-arginine methyl ester, a non-selective nitric oxide synthase inhibitor, and 7-nitro-indazole, a specific inhibitor of neuronal nitric oxide synthase. The above compounds were administered via two routes, i.e. intraperitoneally or locally in the dorsal raphe nucleus, a structure involved in sleep regulation. In order to evaluate their efficiency to inhibit nitric oxide synthesis in the rat brain, they were first administered intraperitoneally to a group of animals, and the cortical release of nitric oxide was determined by means of voltammetric measurements. N-Nitro-L-arginine methyl ester (100 mg/kg, i.p,) did not affect the cortical release of nitric oxide, whereas it increased both slow-wave sleep and paradoxical sleep durations. On the contrary, 7-nitro-indazole (40 mg/kg, i.p.) significantly decreased the cortical release of nitric oxide (- 25%) and paradoxical sleep duration. Furthermore, following microinjection of either N-nitro-L-arginine methyl ester or 7-nitro-indazole at 100 ng/0.20 mu l into the nitric oxidergic cell area of the dorsal raphe nucleus, decreases in paradoxical sleep duration were obtained (- 32.8% and - 25.3%, respectively).The results obtained support the existence of a duality in the sleep regulation modalities exerted by nitric oxide, i.e. a peripheral inhibiting influence and a central facilitating role for the nitric oxide-serotoninergic neurons of the dorsal raphe nucleus. (C) 1999 IBRO. Published by Elsevier Science Ltd.