![]() Adenosine or adenosine receptor agonists enhance sleep –. The endogenous somnogen adenosine is a key mediator of sleep homeostasis. Prolonged wakefulness leads to increased sleep pressure and consequent increased duration and intensity of sleep. Sleep is a homeostatically-regulated process. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was funded by the Wellcome Trust, grant WT087968MA, The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: Nicholas Dale is a founder and shareholder in Sarissa Biomedical. Received: JAccepted: DecemPublished: January 11, 2013Ĭopyright: © 2013 Sims et al. Hôpital du Sacré-Coeur de Montréal, Canada Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state.Ĭitation: Sims RE, Wu HHT, Dale N (2013) Sleep-Wake Sensitive Mechanisms of Adenosine Release in the Basal Forebrain of Rodents: An In Vitro Study. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. ![]() Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. Adenosine release was evoked by high K +, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. The biochemical changes that accompany sleep-wake status may be preserved in vitro. ![]() The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. ![]()
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