Ribeiro, Ana C., and Levente Kapás. Day-and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats. Am J Physiol Regul Integr Comp Physiol 289: R521-R531, 2005. First published April 28, 2005; doi:10.1152/ajpregu.00605.2004.-Previous studies suggest that nitric oxide (NO) may play a role in sleep regulation, particularly in the homeostatic process. The present studies were undertaken to compare the sleep effects of injecting a NO synthase (NOS) inhibitor when homeostatic sleep pressure is naturally highest (light onset) or when it is at its nadir (dark onset) in rats. Sleep, electroencephalogram delta-wave activity during nonrapid eye movement sleep (NREMS), also known as slow-wave activity (SWA), and brain temperature responses to three doses of the NOS inhibitor N -nitro-L-arginine methyl ester (L-NAME; 5, 50, and 100 mg/kg) injected intraperitoneally at light or dark onset were examined in rats (n ϭ 6 to 8). The effects of 5 mg/kg L-NAME were determined in both normal and vagotomized (VX) rats. Light onset administration of 50 mg/kg L-NAME decreased NREMS amounts and suppressed SWA and increased rapid eye movement sleep (REMS) amounts. At dark onset, L-NAME injection also dose dependently suppressed SWA; however, unlike light onset injections, both NREMS and REMS amounts were increased after all three doses. Sleep responses to 5 mg/kg L-NAME were not different in control and VX rats, suggesting that the sleep effects of L-NAME are not mediated through the activation of sensory vagal mechanisms. The present findings suggest that timing of the injection is a major determinant of the sleep responses observed after systemic L-NAME injection in rats.
N-nitro-L-arginine methyl ester; slow-wave activity; homeostatic regulation; vagotomy; suprachiasmatic nucleus; thermoregulation; electroencephalogram power spectrum SLEEP REGULATION RELIES ON the interplay between the homeostatic and circadian processes (5). The homeostatic component manifests itself as an increasing sleep pressure due to prior waking periods, whereas the circadian component is an oscillating process that permits sleep to occur only during low sleep threshold periods. Normally, increased homeostatic pressure coincides with periods of decreased sleep threshold, thus allowing sleep to occur. In nocturnal animals, such as rats, this occurs at the beginning of the light period. A growing number of studies suggest that nitric oxide (NO)-ergic mechanisms play a role in sleep regulation, particularly in the homeostatic component.The two-process model of sleep regulation postulates that the homeostatic process relies on a neuronal mechanism, the activity of which increases during wakefulness and is dissipated during sleep (5). There is evidence that the activity of NO-generating mechanisms in the brain stem, thalamus, and cortex fits this pattern. For example, NO is released in an activity-dependent manner from neurons in brain stem areas involved in sleep regulation (29). In rats, cortical (6) and thalamic (49) NO ...