Adenosine in sleep and wakefulness

Sleep propensity increases in the course of wakefulness: the longer the pre vious wakefulness period is, the longer and deeper (measured as delta power in EEG recordings) is the following sleep. The mechanisms that regulate th e need of sleep at the cellular level are largely unknown. The inhibitory n euromodulator, adenosine, is a promising candidate for a sleep-inducing fac tor: its concentration is higher during wakefulness than during sleep, it a ccumulates in the brain during prolonged wakefulness, and local perfusions as well as systemic administration of adenosine and its agonists induce sle ep and decrease wakefulness. Adenosine receptor antagonists, caffeine and t heophylline, are widely used as stimulants of the central nervous system to induce vigilance and increase the time spent awake. Our hypothesis is that adenosine accumulates in the extracellular space of the basal forebrain du ring wakefulness, increasing the sleep propensity. The increase in extracel lular adenosine concentration decreases the activity of the wakefulness-pro moting cell groups, especially the cholinergic cells in the basal forebrain . When the activity of the wakefulness-active cells decreases sufficiently sleep is initiated. During sleep the extracellular adenosine concentrations decrease, and thus the inhibition of the wakefulness-active cells also dec reases allowing the initiation of a new wakefulness period.