Effects of Long-Term Caffeine Consumption on the Adenosine A Receptor in the Rat Brain: an In Vivo PET Study with [F]CPFPX.

PURPOSE

Caffeine, a nonselective antagonist of adenosine receptors, is the most popular psychostimulant worldwide. Recently, a protective role of moderate chronic caffeine consumption against neurodegenerative diseases such as Alzheimer's and Parkinson's disease has been discussed. Thus, aim of the present study was an in vivo investigation of effects of long-term caffeine consumption on the adenosine A receptor (AAR) in the rat brain.

PROCEDURES

Sixteen adult, male rats underwent five positron emission tomography (PET) scans with the highly selective AAR radioligand [F]CPFPX in order to determine AAR availability. After the first baseline PET scan, the animals were assigned to two groups: Caffeine treatment and control group. The caffeine-treated animals received caffeinated tap water (30 mg/kg bodyweight/day, corresponding to 4-5 cups of coffee per day in humans) for 12 weeks. Subsequently, caffeine was withdrawn and repeated PET measurements were performed on day 1, 2, 4, and 7 of caffeine withdrawal. The control animals were measured according to the same time schedule.

RESULTS

At day 1, after 4.4 h of caffeine withdrawal, a significant decrease (- 34.5%, p < 0.001) of whole brain AAR availability was observed. Unlike all other investigated brain regions in caffeine-treated rats, the hypothalamus and nucleus accumbens showed no significant intraindividual differences between baseline and first withdrawal PET scan. After approximately 27 h of caffeine withdrawal, the region- and group-specific effects disappeared and AAR availability settled around baseline.

CONCLUSIONS

The present study provides evidence that chronic caffeine consumption does not lead to persistent changes in functional availability of cerebral AARs which have previously been associated with neuroprotective effects of caffeine. The acute and region-specific decrease in cerebral AAR availability directly after caffeine withdrawal is most likely caused by residual amounts of caffeine metabolites disguising an unchanged AAR expression at this early time-point.