Recovery sleep after extended wakefulness restores elevated A 1 adenosine receptor availability in the human brain

Significance Our study reveals that prolonged sleep deprivation is accompanied by an A 1 adenosine receptor (A 1 AR) upregulation in the human brain. Recovery sleep quickly restores A 1 AR availability to control levels. High individual A 1 AR availability is related to a low sleep pressure and good cognitive performance. Sleep deprivation is an efficient but short-lasting therapeutic strategy in depression. A causal sleep–wake dysregulation has been proposed, possibly mediated by cerebral adenosine and its A 1 AR. The restoration of the A 1 AR availability after recovery from sleep deprivation mimics the rapid relapse following the end of therapeutic sleep deprivation. Understanding the adenosine regulation under sleep restriction, especially regarding individual characteristics, might improve the rationale for the individual indication and design of therapeutic sleep modulation in depression.