Local energy depletion in the basal forebrain increases sleep

• Published in: The European journal of neuroscience Vol. 17; no. 4; pp. 863 - 869
• Main Authors: Kalinchuk, Anna V., Urrila, Anna-Sofia, Alanko, Lauri, Heiskanen, Silja, Wigren, Henna-Kaisa, Suomela, Maricel, Stenberg, Dag, Porkka-Heiskanen, Tarja
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.02.2003
• Subjects: 2,4-Dinitrophenol - pharmacology; adenosine; Adenosine - metabolism; Analysis of Variance; Animals; basal forebrain; Chromatography, High Pressure Liquid - methods; Circadian Rhythm - physiology; Dose-Response Relationship, Drug; Electroencephalography - methods; Energy Metabolism - drug effects; Energy Metabolism - physiology; Enzyme Inhibitors - pharmacology; Lactic Acid - metabolism; local energy depletion; Male; Microdialysis - methods; non-REM sleep; Potassium Cyanide - pharmacology; Prosencephalon - drug effects; Prosencephalon - metabolism; Pyruvic Acid - metabolism; Rats; Sleep - drug effects; Sleep - physiology; sleep deprivation; Sleep Deprivation - metabolism; Sleep Stages - drug effects; Sleep Stages - physiology; Uncoupling Agents - pharmacology
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1046/j.1460-9568.2003.02532.x

Sleep saves energy, but can brain energy depletion induce sleep? We used 2,4‐dinitrophenol (DNP), a molecule which prevents the synthesis of ATP, to induce local energy depletion in the basal forebrain of rats. Three‐hour DNP infusions induced elevations in extracellular concentrations of lactate, pyruvate and adenosine, as well as increases in non‐REM sleep during the following night. Sleep was not affected when DNP was administered to adjacent brain areas, although the metabolic changes were similar. The amount and the timing of the increase in non‐REM sleep, as well as in the concentrations of lactate, pyruvate and adenosine with 0.5–1.0 mm DNP infusion, were comparable to those induced by 3 h of sleep deprivation. Here we show that energy depletion in localized brain areas can generate sleep. The energy depletion model of sleep induction could be applied to in vitro research into the cellular mechanisms of prolonged wakefulness.