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Br J Pharmacol. 2012 Mar;165(6):1904-1913. doi: 10.1111/j.1476-5381.2011.01689.x.

Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation.

Author information

1
Institute of Pharmacology and Toxicology, University of Zürich, Zürich, SwitzerlandDepartment of Psychiatry, University of Münster, Münster, GermanyDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Johann-Wolfgang Goethe University, Frankfurt am Main, GermanyDepartment of Psychiatry, University of Würzburg, Würzburg, GermanyZürich Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.

Abstract

BACKGROUND AND PURPOSE:

Prolonged wakefulness impairs sustained vigilant attention, measured with the psychomotor vigilance task (PVT), and induces a compensatory increase in sleep intensity in recovery sleep, quantified by slow-wave activity (SWA) in the sleep electroencephalogram (EEG). These effects of sleep deprivation are counteracted by the adenosine receptor antagonist caffeine, implying involvement of the adenosine neuromodulator/receptor system. To examine a role for adenosine A(2A) receptors, we investigated whether variation of the A(2A) receptor gene (ADORA2A) modified effects of caffeine on PVT and SWA after sleep deprivation.

EXPERIMENTAL APPROACH:

A haplotype analysis of eight single-nucleotide polymorphisms of ADORA2A was performed in 82 volunteers. In 45 young men carrying five different allele combinations, we investigated the effects of prolonged waking and 2 × 200 mg caffeine or 2 × 100 mg modafinil on psychomotor vigilance, sleepiness, and the waking and sleep EEG.

KEY RESULTS:

Throughout extended wakefulness, the carriers of haplotype HT4 performed faster on the PVT than carriers of non-HT4 haplotype alleles. In haplotype HT4, caffeine failed to counteract the waking-induced impairment of PVT performance and the rebound of SWA in recovery sleep. However, caffeine was effective in non-HT4 allele carriers, and modafinil reduced the consequences of prolonged waking, independently of ADORA2A haplotype.

CONCLUSIONS AND IMPLICATIONS:

Common genetic variation of ADORA2A is an important determinant of psychomotor vigilance in rested and sleep-deprived state. It also modulates individual responses to caffeine after sleep deprivation. These findings demonstrate a role for adenosine A(2A) receptors in the effects of prolonged wakefulness on vigilant attention and the sleep EEG.

PMID:
21950736
PMCID:
PMC3372839
DOI:
10.1111/j.1476-5381.2011.01689.x
[Indexed for MEDLINE]
Free PMC Article

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