Chronic sleep loss and A1 adenosine receptors in the human brain

STUDY OBJECTIVES: The cerebral adenosinergic system is involved in sleep-wake regulation and presumably represents a neuro-molecular correlate of homeostatic sleep pressure. For acute sleep deprivation, it has been shown that increased cerebral A1 adenosine receptor (A1AR) availability was related to impairments in cognitive performance. The present study examined A1AR availability in response to chronic sleep restriction and recovery. METHODS: To quantify A1AR availability we used 8-Cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine ([18F] CPFPX) positron emission tomography in 21 volunteers after 5 nights with 5-h sleep opportunities followed by 8 h recovery sleep. Data were compared to a control group of 15 volunteers who slept 8 h each night. In addition, polysomnography, cognitive performance, and alertness were recorded. RESULTS: Chronic sleep restriction did not increase the A1AR availability. Slow wave sleep (SWS) and EEG slow-wave-activity (SWA) in the first 5 h of sleep did not differ from baseline (BL), but SWA in the last 3 h of sleep was increased and cognitive performance and alertness were impaired. While SWA returned to BL in the last 3 h of recovery sleep, performance, and alertness remained impaired. CONCLUSION: The results indicate that chronic sleep loss likely induces parallel upregulations of extracellular adenosine and A1AR resulting in no net gain in receptor availability. The results contrast with findings from acute sleep deprivation in which we found impaired performance and increased A1AR availability that were restored to rested levels after recovery sleep. The findings reveal fundamental differences in the mechanisms through which acute and chronic sleep loss affect adenosinergic regulation and cognitive performance.