title: Local energy depletion in the basal forebrain increases sleep.
abstract: 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.
authors.affiliation: Department of Physiology, Institute of Biomedicine, PO Box 63, 00014 University of Helsinki, Finland.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Kalinchuk
authors.forename: Anna-Sofia
authors.initials: AS
authors.lastname: Urrila
authors.forename: Lauri
authors.initials: L
authors.lastname: Alanko
authors.forename: Silja
authors.initials: S
authors.lastname: Heiskanen
authors.forename: Henna-Kaisa
authors.initials: HK
authors.lastname: Wigren
authors.forename: Maricel
authors.initials: M
authors.lastname: Suomela
authors.forename: Dag
authors.initials: D
authors.lastname: Stenberg
authors.forename: Tarja
authors.initials: T
authors.lastname: Porkka-Heiskanen
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002940:Circadian Rhythm / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D011190:Potassium Cyanide / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014475:Uncoupling Agents; D019344:Lactic Acid; D019289:Pyruvic Acid; D000241:Adenosine; D011190:Potassium Cyanide; D019297:2,4-Dinitrophenol