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


Bodenmann, S; Hohoff, C; Freitag, C; Deckert, J; Rétey, J V; Bachmann, V; Landolt, H-P (2012). Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioral performance and sleep EEG after sleep deprivation. British Journal of Pharmacology, 165(6):1904-1913.

Abstract

Background and purpose:  Prolonged wakefulness impairs sustained vigilant attention as measured with the psychomotor vigilance task (PVT) and induces a compensatory increase in sleep intensity in recovery sleep as quantified by slow-wave activity (SWA) in the sleep electroencephalogram (EEG). These effects of sleep deprivation are counteracted by the adenosine receptor antagonist caffeine, suggesting that the adenosine neuromodulator/receptor system is importantly involved. To examine a role for A(2A) receptors, we investigated whether variation of the A(2A) receptor gene (ADORA2A) modulates the effects of caffeine on PVT and SWA after sleep deprivation. Experimental approach:  We performed in 82 volunteers a haplotype analysis of 8 single nucleotide polymorphisms of ADORA2A. In 45 young men carrying 5 different allele combinations, we investigated the effects of prolonged waking and 2 x 200 mg caffeine or 2 x 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. By contrast, 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 A(2A) receptors in the effects of prolonged wakefulness on vigilant attention and the sleep EEG.

Abstract

Background and purpose:  Prolonged wakefulness impairs sustained vigilant attention as measured with the psychomotor vigilance task (PVT) and induces a compensatory increase in sleep intensity in recovery sleep as quantified by slow-wave activity (SWA) in the sleep electroencephalogram (EEG). These effects of sleep deprivation are counteracted by the adenosine receptor antagonist caffeine, suggesting that the adenosine neuromodulator/receptor system is importantly involved. To examine a role for A(2A) receptors, we investigated whether variation of the A(2A) receptor gene (ADORA2A) modulates the effects of caffeine on PVT and SWA after sleep deprivation. Experimental approach:  We performed in 82 volunteers a haplotype analysis of 8 single nucleotide polymorphisms of ADORA2A. In 45 young men carrying 5 different allele combinations, we investigated the effects of prolonged waking and 2 x 200 mg caffeine or 2 x 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. By contrast, 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 A(2A) receptors in the effects of prolonged wakefulness on vigilant attention and the sleep EEG.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2012
Deposited On:18 Nov 2011 08:33
Last Modified:03 Aug 2017 15:34
Publisher:Wiley-Blackwell
ISSN:0007-1188
Additional Information:The definitive version is available at www.interscience.wiley.com
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/j.1476-5381.2011.01689.x
PubMed ID:21950736

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