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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Deckert, J. Rétey, J. V. Freitag, C. Bachmann, V. Bodenmann, S. Landolt, H-p Hohoff, C. |
| Description | Author Affiliation: Bodenmann S ( Institute of Pharmacology and Toxicology, 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 165 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2012-03-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Caffeine Pharmacology Central Nervous System Stimulants Purinergic P1 Receptor Antagonists Receptor, Adenosine A2A Genetics Sleep Deprivation Attention Drug Effects Benzhydryl Compounds Cross-Over Studies Double-Blind Method Electroencephalography Polymorphism, Single Nucleotide Psychomotor Performance Physiopathology Wakefulness Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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