Does repeated coffee consumption during chronic sleep restriction affect A1 adenosine receptor availability in humans?

Objectives:Adenosine and cerebral adenosine A1 (A1AR) and A2A receptors are important modulators of the sleep-wake cycle and regulate to some extent the sleep-wake homeostasis. Acute sleep deprivation has been shown to result in an upregulation of A1ARs in human and rat brains. The stimulating effects of caffeine are evoked through non-selective antagonism at adenosine receptors. Using positron emission tomography (PET), we investigate the effect of repeated coffee consumption during chronic sleep restriction and subsequent coffee abstinence after recovery sleep on cerebral A1AR availability and occupancy in humans.Methods:Thirty healthy volunteers (28±5 years, 15f) completed an in-lab study including three [18F]CPFPX PET scans to determine cerebral A1AR availability after subsequent exposure to rested (3 nights with 8h time in bed (TIB)), chronically sleep restricted (5 nights with 5h TIB), and recovery (one night with 8h TIB) conditions. Participants either consumed freshly brewed coffee (n = 17) or decaffeinated coffee (n = 13) during 5 days of sleep restriction (prior caffeine abstinence > 10 days). Regular coffee contained 200 mg caffeine at 7.30 a.m. and 100 mg caffeine at 2.00 p.m., decaffeinated coffee contained 4 mg and 2 mg, respectively. PET scans were conducted at the same time of day under caffeine-abstinent rested conditions, roughly 7h after the latest coffee intake after sleep restriction, and after ~ 31h of coffee abstention after recovery. Caffeine levels in saliva were determined repeatedly. Cerebral A1AR availability was quantified by distribution volume (VT) and occupancy levels were calculated by applying the Lassen plot including cortical and subcortical areas, cerebellum, and pons.Results:In the decaffeinated coffee group, no differences in cerebral A1AR availability were found between baseline condition, 5 days of sleep restriction and one night of recovery sleep. Repeated administration of regular coffee resulted in a displacement of [18F]CPFPX binding of 19 ± 13 % on average. One day after coffee abstention and recovery sleep, VT values did not differ from baseline.Conclusions:Our data suggest that neither chronic sleep restriction for 5 days nor combination with repeated caffeine consumption result in a persistent change in the regulation of cerebral A1AR availability.Financial support:The work was supported by the Institute for Scientific Information on Coffee, the Swiss National Science Foundation (# 320030_163439) and respective institutional funds.