Positive feedback from coffee

摘要

Have you ever wondered why coffee is such an effective pick-me-up? The answer has been gradually coming into focus over the past few years, thanks to numerous studies of the brain regions and neuronal molecules affected. With the work reported by Lindskog and colleagues on page 774 of this issue, much of the fine detail has been filled in. In broad terms, the effects of caffeine on the body have been known for several years. At the concentrations reached during habitual coffee consumption, caffeine is thought to bind to and block two proteins ―the A_1 and A_(2A) receptors―on the surface of certain nerve cells that control voluntary movements. This means that the receptors can no longer detect the neuromodulator adeno-sine, which results in a long-lasting decrease in the activity of inhibitory neurons, and hence more movement, in rodents. Early evidence for this theory came in 1995, when Svenningsson, Nomikos and Fredholm found that the stimulatory effects of caffeine are strongly correlated with the reduced expression of certain genes that would normally be switched on in response to activation of the A_(2A) receptor by adeno-sine. More support came from studies of mice engineered to lack this receptor. Moreover, A_(2A)-receptor blockers are being developed as potential treatments for Parkinson's disease, and there is evidence that caffeine can help to protect against the nerve degeneration associated with this disease. So the idea that caffeine works by blocking the A_(2A) receptors seems well established.