Adenosinergic Control of Sleep/Wake Behavior

Adenosine is formed by various processes in all cell types, and its basal level depends only on the fundamental mechanisms of cell biology. Therefore, adenosine in the central nervous system is not a neurotransmitter or a typical neuromodulator, but rather functions as an autacoid, a biological factor that acts near the site of synthesis, where it is also rapidly metabolized. Surprisingly, although adenosine has long been studied as a sleep-promoting substance, the source of adenosine and the brain regions where adenosine receptors control sleep/wake behavior are poorly understood. In this chapter, we present an overview of current knowledge regarding the regulation of sleep and wake by adenosine. As knowledge of the molecular and circuit bases of sleep/wake regulation expands, new roles of adenosine receptors in modulating different aspects of sleep emerge. For example, A2A receptors appear to gate sleep by suppressing arousal, whereas sleep need is mediated by A1 receptors, and these receptors may thus play a crucial role in the function of sleep.