Inhibition of nitric oxide synthesis inhibits rat sleep

Previous findings indicate that nitric oxide (NO) may play a role in the regulation of sleep-wake activity. In rabbits, blocking the production of endogenous NO by a nitric oxide synthase inhibitor, Nω-nitro-l-arginine (l-NAME) suppresses spontaneous sleep and interferes the somnogenic actions of interleukin 1. In the present experiments we extended our earlier work by studying the long-term effects of l-NAME treatment on sleep-wake activity including power spectra analyses of the electroencephalogram (EEG) in rats. Rats implanted with EEG electrodes, brain thermistor, and intracerebroventricular (i.c.v.) guide cannula were injected i.c.v. with vehicle or 0.2, 1, or 5 mg l-NAME at light onset. In separate experiments, rats were injected intraperitoneally (i.p.) with l-NAME three times (50, 50, 100 mg/kg), 12-12 h apart. Both i.c.v. and i.p. injections of l-NAME elicited decreases in time spent in NREMS and REMS. After i.c.v. injection of 5 mg l-NAME the sleep responses were long-lasting; NREMS did not return to baseline even 72 h after injection. EEG delta-wave activity during NREMS (slow wave activity) was also suppressed after 0.2 and 5 mg l-NAME. Brain temperature was slightly increased after the two lower doses of l-NAME, whereas there was a transient decrease in T_br after 5 mg l-NAME. Acute i.p. injection of 50 mg/kg l-NAME elicited an immediate decrease in NREMS which lasted for ∼ 2 h. The second injection of 50 mg/kg l-NAME and the following injection of 100 mg/kg l-NAME induced biphasic decreases in NREMS but not REMS. These results are in accordance with our earlier observations that inhibition of nitric oxide synthesis suppresses spontaneous sleep and are consistent with the hypothesis that NO is involved in the maintenance of normal sleep-wake activity.