Recovery sleep after extended wakefulness restores elevated A₁ adenosine receptor availability in the human brain

Adenosine and functional A₁ adenosine receptor (A₁AR) availability are supposed to mediate sleep-wake regulation and cognitive performance. We hypothesized that cerebral A₁AR availability after an extended wake period decreases to a well-rested state after recovery sleep. [¹⁸F]CPFPX positron emission tomography was used to quantify A₁AR availability in 15 healthy male adults after 52 h of sleep deprivation and following 14 h of recovery sleep. Data were additionally compared with A₁AR 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 A₁AR availability in several brain regions, ranging from 11% (insula) to 14% (striatum). A₁AR 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 A₁AR availability. Sleep deprivation resulted in a higher A₁AR 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 A₁AR availability were more resilient to sleep-loss effects than those with a subtle increase. This pattern implies that differences in endogenous adenosine and A₁AR availability might be causal for individual responses to sleep loss.