Researchers used PET to visualize binding sites of caffeine in the living human brain, making it possible to explore effects of caffeine consumption.
For the first time, researchers have been able to use positron emission tomography (PET) to visualize binding sites of caffeine in the living human brain, making it possible to explore possible effects of caffeine consumption.
Caffeine, a neuroactive agent, is one of the most commonly consumed psychoactive substances worldwide. Caffeine has also been found to have some protection against some neurodegenerative diseases. In the U.S., it is estimated that 80 percent of adults consume an average of 200 mg of caffeine daily, the equivalent of two 5-ounce cups of coffee or four sodas.
But until now, researchers have not been able to visualize or quantify the effect of caffeine on the brain. In vitro studies have shown that commonly consumed quantities of caffeine have led to high A1 adenosine in the brain, David Elmenhorst, MD, lead author of a study published in the November issue of The Journal of Nuclear Medicine, said in a press release. The A1 adenosine receptor is the most abundant in the human brain. Researchers sought to measure the A1 adenosine receptor occupancy with in vivo imaging.
Fifteen male volunteers, aged 24 to 68, underwent PET scanning with 18F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (F-18-CPFPX) after 36 hours of abstaining from caffeine intake. Following the scan, the subjects received 10-minute infusions of caffeine of varying concentrations based on their body weight. One subject received an intravenous placebo instead of caffeine.
To estimate the occupancy of A1 adenosine receptors by caffeine, the distribution volume at the baseline period of the PET scan was compared with the distribution volume after caffeine administration. The concentration of the caffeine that displaces 50 percent of the binding of F-18-CPFPX to the A1 adenosine receptor was 13 mg/L, or about four to five cups of coffee. About half of the A1 adenosine receptors may be occupied by caffeine in most regular coffee drinkers, noted the authors. This could lead to adaptive changes and chronic alterations of receptor express and availability.
“Several investigations show that moderate coffee consumption of three to five cups per day at mid-life is linked to a reduced risk of dementia in late life,” said Elmenhorst. “The present study provides evidence that typical caffeine doses result in a high A1 adenosine receptor deserves broader attention in the context of neurodegenerative disorders.”
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