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.