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 eater (L-NAME), a Competitive inh ibitor of enzyme nitric oxide synthase (NOS), on spontaneous sleep during t he light period, was studied in adult rats implanted for chronic sleep reco rdings. L-NAME was injected by subcutaneous (s.c.) or intracerebroventricul ar (i.c.v.) routes or was infused directly into the dorsal raphe nuclei (DR N). 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-ey e-movement sleep (REMS) during the first 3 h of recording. On the other han d, direct application of L-NAME into the DRN (50.0-150.0 mu g) induced an i ncrement 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 t he 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 red uction of acetylcholine release in areas critical for REMS promotion. A dec rease in gamma-aminobutyric acid (GABA) release after nitric oxide synthesi s inhibition could play a role in the reduction of SWS. (C) 1999 Elsevier S cience B.V. All rights reserved.