Day- and nighttime injection of a nitric oxide synthase inhibitor elicits opposite sleep responses in rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 289; no. 2; pp. R521 - R531
• Main Authors: Ribeiro, Ana C, Kapas, Levente
• Format: Journal Article
• Language: English
• Published: United States 01.08.2005
• Subjects: Animals; Body Temperature - drug effects; Brain - physiology; Circadian Rhythm; Dose-Response Relationship, Drug; Drug Administration Schedule; Electroencephalography; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - pharmacology; Male; NG-Nitroarginine Methyl Ester - administration & dosage; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; Sleep - drug effects; Sleep - physiology; Sleep Stages - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00605.2004

Department of Biological Sciences, Fordham University, Bronx, New York Submitted 7 September 2004 ; accepted in final form 21 April 2005 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 = 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 Address for reprint requests and other correspondence: L. Kapás, Dept. of Biological Sciences, Fordham Univ., 441 E. Fordham Rd., Bronx, NY 10458 (e-mail: kapas{at}fordham.edu )