Endogenous nitric oxide in the rat pons promotes sleep.
Pontine cholinergic structures are known to play a key role in the regulation of vigilance states associated with desynchronised EEG, i. e., wakefulness and paradoxical sleep. As the cholinergic cells of these nuclei, the pedunculopontine tegmentum (PPT) and the laterodorsal tegmentum, are enriched with nitric oxide synthase (NOS), we tested the hypothesis that nitric oxide (NO) in the pons is implicated in wake and sleep regulation. For this reason, a NOS inhibitor, a NO precursor and a NO donor were injected in the PPT of rats. Vigilance states were recorded for 6 h following the injections. Quantification of vigilance states after drug injections were compared to those obtained in control conditions. It appeared that the NO donor had a slight effect on vigilance states, but the NOS inhibitor decreased sleep and inversely the NO precursor increased sleep. These results show for the first time in the rat that a NOS inhibitor, injected directly into the PPT, is able to reduce sleep and that a NO precursor had the opposite effect. They suggest that endogenous NO production in the PPT has a somnogenic effect. The participation of endogenous NO in vigilance regulation is discussed in light of the role attributed to pontine cholinergic system in wakefulness and sleep.
Hars
B
B
Laboratoire de Neurobiologie de l'Apprentissage et de la Mémoire, URA CNRS 1491, Universté Paris-sud, Bât. 445, 91405 Orsay Cedex, France. bernard.hars@ibaic.u-psud.fr
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D008297:Male; D008845:Microinjections; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D011149:Pons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000187:drug effects*; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
D000813:Anilides; D009569:Nitric Oxide; C002385:linsidomine; C080840:N(G)-nitroarginine-4-nitroanilide; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat