Effects of Long-Term Caffeine Consumption on the Adenosine A1 Receptor in the Rat Brain: an In Vivo PET Study with [18F]CPFPX
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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 A1 receptor (A1AR) in the rat brain.
Sixteen adult, male rats underwent five positron emission tomography (PET) scans with the highly selective A1AR radioligand [18F]CPFPX in order to determine A1AR 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 Subsequently, caffeine was withdrawn and repeated PET measurements were performed on day 1, 2, 4, and 7 of caffeine withdrawal.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.
At day 1, after 4.4 h of caffeine withdrawal, a significant decrease (− 34.5%, p < 0.001) of whole brain A1AR 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 A1AR availability settled around baseline.
The present study provides evidence that chronic caffeine consumption does not lead to persistent changes in functional availability of cerebral A1ARs which have previously been associated with neuroprotective effects of caffeine. The acute and region-specific decrease in cerebral A1AR availability directly after caffeine withdrawal is most likely caused by residual amounts of caffeine metabolites disguising an unchanged A1AR expression at this early time-point.
Key WordsChronic caffeine PET Adenosine A1 receptor Rat Brain
Tim Urbansky, Andrea Radermacher, Sylvia Köhler-Dibowski, Stefanie Krause, and Dorothe Krug are gratefully acknowledged for excellent technical assistance. We thank Daniela Schneider for analyzing plasma caffeine concentrations, Nikola Kornadt-Beck for fruitful discussions and valuable support, and Johannes Ermert and Bernd Neumaier for radioligand supply.
Compliance with Ethical Standards
All experiments were approved by the regional authorities and conducted in accordance with the German Animal Protection Act.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 26.Kaplan GB, Greenblatt DJ, Kent MA et al (1993) Caffeine treatment and withdrawal in mice: relationships between dosage, concentrations, locomotor activity and A1 adenosine receptor binding. J Pharamcol Exp Ther 266:1563–1572Google Scholar
- 34.Liu X, Smith BJ, Chen C et al (2005) Use of a physiologically based pharmacokinetic model to study the time to reach brain equilibrium: an experimental analysis of the role of blood-brain barrier permeability, plasma protein binding, and brain tissue binding. J Pharmacol Exp Ther 313:1254–1262CrossRefPubMedGoogle Scholar