Pontine injections of nitric oxide synthase inhibitor l-name consolidate episodes of rem sleep in the rat.
Dorsal mesopontine cholinergic neurons control rapid eye movement sleep (REMS) and wakefulness and contain nitric oxide (NO) synthase. To assess whether local inhibition of NO synthase has distinct effects on sleep, N-nitro-L-arginine methyl ester, an NO synthesis inhibitor (L-NAME, 80 mM), carbachol, a cholinergic agonist (2, 10 or 50 mM), or saline were microinjected (120-200 nl) into the dorsal mesopontine tegmentum in rats. Sleep-wake cycles were monitored during the subsequent 6 h periods. Compared to control injections, L-NAME changed the pattern of REMS by prolonging individual episodes with a small increase in the percentage time of REMS and no change in slow wave sleep (SWS). Carbachol, at 50 mM, enhanced wakefulness and suppressed both SWS and REMS, especially during the first 2 h post-injection. At the two lower concentrations, carbachol moderately enhanced REMS 2-6 h post-injection by increasing the frequency, rather than duration, of individual episodes. Thus, a reduced NO release in the dorsal pontine tegmentum has a powerful consolidating effect on REMS episodes, whereas the direction of the effect of carbachol on the amount of sleep, and REMS in particular, depends on the magnitude of cholinergic stimulation. The REMS-consolidating effects of NO synthase inhibition in the pons may result from modulatory effects of NO on the release of acetylcholine and other neurotransmitters within the dorsal mesopontine tegmentum.
Okabe
S
S
Center for Sleep and Respiratory Neurobiology, Department of Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Sanford
L D
LD
Veasey
S C
SC
Kubin
L
L
D000704:Analysis of Variance; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011149:Pons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester