1. ¹Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland
2. ²Department of Neurology, University Hospital, Zürich, Switzerland
3. ³Institute of Medical Genetics, University of Zürich, Zürich, Switzerland
4. ⁴Zürich Center for Integrative Human Physiology (ZIHP), University of Zürich, Zürich, Switzerland

Correspondence: H-P Landolt, (landolt@pharma.unizh.ch)

Received 26 October 2006; Accepted 23 December 2006; Published online 28 February 2007.

Abstract

Caffeine is the most widely used stimulant in Western countries. Some people voluntarily reduce caffeine consumption because it impairs the quality of their sleep. Studies in mice revealed that the disruption of sleep after caffeine is mediated by blockade of adenosine A_2A receptors. Here we show in humans that (1) habitual caffeine consumption is associated with reduced sleep quality in self-rated caffeine-sensitive individuals, but not in caffeine-insensitive individuals; (2) the distribution of distinct c.1083T>C genotypes of the adenosine A_2A receptor gene (ADORA2A) differs between caffeine-sensitive and -insensitive adults; and (3) the ADORA2A c.1083T>C genotype determines how closely the caffeine-induced changes in brain electrical activity during sleep resemble the alterations observed in patients with insomnia. These data demonstrate a role of adenosine A_2A receptors for sleep in humans, and suggest that a common variation in ADORA2A contributes to subjective and objective responses to caffeine on sleep.