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

Autor: Michael Sommerauer, Christian R. Baumann, Sebastian C. Holst, Alessandro Borrello, Susanne Weigend, Wolfgang Berger, Thomas Müller, Hans-Peter Landolt, Amandine Valomon
Přispěvatelé: University of Zurich, Landolt, Hans-Peter
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Genotype
10050 Institute of Pharmacology and Toxicology
610 Medicine & health
Placebo
Catechol O-Methyltransferase
Polymorphism
Single Nucleotide
Article
03 medical and health sciences
11124 Institute of Medical Molecular Genetics
2738 Psychiatry and Mental Health
Young Adult
0302 clinical medicine
Dopamine
Internal medicine
medicine
Humans
Attention
Prefrontal cortex
Pharmacology
Tolcapone
business.industry
Dopaminergic
Catechol O-Methyltransferase Inhibitors
Sleep in non-human animals
10040 Clinic for Neurology
Sleep deprivation
Psychiatry and Mental health
030104 developmental biology
Endocrinology
3004 Pharmacology
10076 Center for Integrative Human Physiology
570 Life sciences
biology
Sleep Deprivation
Wakefulness
medicine.symptom
business
030217 neurology & neurosurgery
medicine.drug
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 43(7)
ISSN: 1740-634X
Popis: 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, COMT genotype and tolcapone modulated the sleep loss-induced impairment of vigilant attention. More specifically, Val/Met heterozygotes produced twice as many lapses after a night without sleep than Met/Met homozygotes. Unexpectedly, tolcapone further deteriorated the sleep loss-induced performance deficits when compared to placebo, particularly in Val/Met and Met/Met genotypes. The findings suggest that PFC dopaminergic tone regulates sustained attention after sleep loss according to an inverse U-shape relationship, independently of neurophysiological markers of elevated sleep need.
Databáze: OpenAIRE
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