Nitric oxide and sleep in the rat: A puzzling relationship

To date, only a few studies indicate that nitric oxide may play a role in t he regulation of the sleep-wake cycle. However, data reported are controver sial and the pan played by nitric oxide in sleep-wake cycle regulation stil l remains uncertain. In the present report, we studied the effects on sleep amounts of two different nitric oxide synthase inhibitors: N-nitro-L-argin ine methyl ester, a non-selective nitric oxide synthase inhibitor, and 7-ni tro-indazole, a specific inhibitor of neuronal nitric oxide synthase. The a bove compounds were administered via two routes, i.e. intraperitoneally or locally in the dorsal raphe nucleus, a structure involved in sleep regulati on. In order to evaluate their efficiency to inhibit nitric oxide synthesis in the rat brain, they were first administered intraperitoneally to a grou p of animals, and the cortical release of nitric oxide was determined by me ans of voltammetric measurements. N-Nitro-L-arginine methyl ester (100 mg/k g, i.p,) did not affect the cortical release of nitric oxide, whereas it in creased both slow-wave sleep and paradoxical sleep durations. On the contra ry, 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-n itro-indazole at 100 ng/0.20 mu l into the nitric oxidergic cell area of th e dorsal raphe nucleus, decreases in paradoxical sleep duration were obtain ed (- 32.8% and - 25.3%, respectively). The results obtained support the existence of a duality in the sleep regula tion modalities exerted by nitric oxide, i.e. a peripheral inhibiting influ ence and a central facilitating role for the nitric oxide-serotoninergic ne urons of the dorsal raphe nucleus. (C) 1999 IBRO. Published by Elsevier Sci ence Ltd.