Role of nitric oxide in sleep regulation: effects of L-NAME, an inhibitor of nitric oxide synthase, on sleep in rats.
The effect of N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of enzyme nitric oxide synthase (NOS), on spontaneous sleep during the light period, was studied in adult rats implanted for chronic sleep recordings. L-NAME was injected by subcutaneous (s.c.) or intracerebroventricular (i.c.v.) routes or was infused directly into the dorsal raphe nuclei (DRN). Subcutaneous (1.25-5.0 mg/kg) or i.c.v. (0.25-1.0 mg) administration of L-NAME increased waking (W) and reduced slow wave sleep (SWS) and rapid-eye-movement sleep (REMS) during the first 3 h of recording. On the other hand, direct application of L-NAME into the DRN (50.0-150.0 microg) induced an increment of W and a reduction of SWS without suppressing REMS. Values of W and SWS were significantly different compared with those of controls during the 6-h recording period. The effects of L-NAME observed after s.c. or i.c.v. administration confirm previous studies in rabbits and rats, in which the NOS inhibitor reduced sleep and increased W in a dose-dependent manner. It is possible that REMS suppression after L-NAME could be related to a reduction of acetylcholine release in areas critical for REMS promotion. A decrease in gamma-aminobutyric acid (GABA) release after nitric oxide synthesis inhibition could play a role in the reduction of SWS.
Monti
J M
JM
Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, Uruguay. jmonti@chasque.apc.org
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Ponzoni
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Monti
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Banchero
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D000818:Animals; D001921:Brain / Q000187:drug effects; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D011817:Rabbits; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester