Nitric oxide production in the basal forebrain is required for recovery sleep

• Published in: Journal of neurochemistry 2006-10, Vol.99 (2), p.483-498
• Main Authors: Kalinchuk, A. V., Lu, Y., Stenberg, D., Rosenberg, P. A., Porkka‐Heiskanen, T.
• Format: Article
• Language: English
• Subjects: adenosine; Adenosine - metabolism; Ageing, cell death; Animals; basal forebrain; Biochemistry; Biological and medical sciences; Brain; Cell physiology; Diagonal Band of Broca - drug effects; Diagonal Band of Broca - metabolism; Energy Metabolism - drug effects; Energy Metabolism - physiology; Enzyme Inhibitors - pharmacology; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Lactic Acid - metabolism; Male; Medical sciences; Microdialysis; Molecular and cellular biology; Neurology; Neurosciences; Nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Donors - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - metabolism; Prosencephalon - drug effects; Prosencephalon - metabolism; Pyruvic Acid - metabolism; Rats; Rats, Wistar; Recovery of Function - physiology; recovery sleep; Signal transduction; Signal Transduction - physiology; Sleep; Sleep - drug effects; Sleep - physiology; sleep deprivation; Sleep Deprivation - metabolism; Sleep Deprivation - physiopathology; Up-Regulation - drug effects; Up-Regulation - physiology; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2006.04077.x

Sleep homeostasis is the process by which recovery sleep is generated by prolonged wakefulness. The molecular mechanisms underlying this important phenomenon are poorly understood. Here, we assessed the role of the intercellular gaseous signaling agent NO in sleep homeostasis. We measured the concentration of nitrite and nitrate, indicative of NO production, in the basal forebrain (BF) of rats during sleep deprivation (SD), and found the level increased by 100 ± 51%. To test whether an increase in NO production might play a causal role in recovery sleep, we administered compounds into the BF that increase or decrease concentrations of NO. Infusion of either a NO scavenger, 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoline‐1‐oxyl‐3‐oxide, or a NO synthase inhibitor, Nω‐nitro‐l‐arginine methyl ester (L‐NAME), completely abolished non‐rapid eye movement (NREM) recovery sleep. Infusion of a NO donor, (Z)‐1‐[N‐(2‐aminoethyl)‐N‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2diolate (DETA/NO), produced an increase in NREM that closely resembled NREM recovery after prolonged wakefulness. The effects of inhibition of NO synthesis and the pharmacological induction of sleep were effective only in the BF area. Indicators of energy metabolism, adenosine, lactate and pyruvate increased during prolonged wakefulness and DETA/NO infusion, whereas L‐NAME infusion during SD prevented the increases. We conclude that an increase in NO production in the BF is a causal event in the induction of recovery sleep.