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

Adenosine and functional A adenosine receptor (AAR) availability are supposed to mediate sleep-wake regulation and cognitive performance. We hypothesized that cerebral AAR availability after an extended wake period decreases to a well-rested state after recovery sleep. [F]CPFPX positron emission tomography was used to quantify AAR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with AAR values after 8 h of baseline sleep from an earlier dataset. Polysomnography, cognitive performance, and sleepiness were monitored. Recovery from sleep deprivation was associated with a decrease in AAR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). AAR availabilities after recovery did not differ from baseline sleep in the control group. The degree of performance impairment, sleepiness, and homeostatic sleep-pressure response to sleep deprivation correlated negatively with the decrease in AAR availability. Sleep deprivation resulted in a higher AAR availability in the human brain. The increase that was observed after 52 h of wakefulness was restored to control levels during a 14-h recovery sleep episode. Individuals with a large increase in AAR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and AAR availability might be causal for individual responses to sleep loss.