Effects of COMT genotype and tolcapone on lapses of sustained attention after sleep deprivation in healthy young men

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Amandine ValomonHans-Peter Landolt

Abstract

Tolcapone, a brain penetrant selective inhibitor of catechol-O-methyltransferase (COMT) devoid of psychostimulant properties, improves cognition and cortical information processing in rested volunteers, depending on the genotype of the functional Val158Met polymorphism of COMT. The impact of this common genetic variant on behavioral and neurophysiological markers of increased sleep need after sleep loss is controversial. Here we investigated the potential usefulness of tolcapone to mitigate consequences of sleep deprivation on lapses of sustained attention, and tested the hypothesis that dopamine signaling in the prefrontal cortex (PFC) causally contributes to neurobehavioral and neurophysiological markers of sleep homeostasis in humans. We first quantified in 73 young male volunteers the impact of COMT genotype on the evolution of attentional lapses during 40 h of extended wakefulness. Subsequently, we tested in an independent group of 30 young men whether selective inhibition of COMT activity with tolcapone counteracts attentional and neurophysiological markers of elevated sleep need in a genotype-dependent manner. Neither COMT genotype nor tolcapone affected brain electrical activity in wakefulness and sleep. By contrast, CO...Continue Reading

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Methods Mentioned

BETA
Genotyping
PCR
electrophoresis

Clinical Trials Mentioned

NCT02080715

Software Mentioned

Psychology
Sequencing Analysis
MATLAB
SDS
Rembrandt ® Analysis Manager
SAS
Prime
SeqScape

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