51953
document
Polymorphisms of ADORA2A modulate psychomotor vigilance and the effects of caffeine on neurobehavioural performance and sleep EEG after sleep deprivation . 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 .
51954
Intervention_Pharmacological
caffeine
51955
Intervention_Physical
sleep deprivation
51956
Outcome_Mental
neurobehavioural performance and sleep EEG
51957
Outcome_Mental
vigilant attention
51958
Outcome_Other
psychomotor vigilance task ( PVT )
51959
Outcome_Physical
slow-wave activity ( SWA )
51960
Outcome_Physical
sleep electroencephalogram ( EEG )
51961
Outcome_Other
PVT
51962
Outcome_Physical
SWA
51963
Participant_Condition
Polymorphisms of ADORA2A modulate psychomotor vigilance
51964
Participant_Sample-size
82
51965
Participant_Sample-size
45
51966
Participant_Age
young
51967
Participant_Sex
men
51968
Participant_Condition
five different allele combinations
51969
Participant_Condition
prolonged waking and 2 × 200 mg caffeine or 2 × 100 mg modafinil on psychomotor