Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6298
Bodenmann, S; Xu, S; Luhmann, U; Arand, M; Berger, W; Jung, H; Landolt, H P (2009). Pharmacogenetics of Modafinil after sleep loss: Catechol-O-methyltransferase genotype modulates waking functions but not recovery sleep. Clinical Pharmacology and Therapeutics, 85(3):296-304.
Sleep loss impairs waking functions and is homeostatically compensated in recovery sleep. The mechanisms underlying the consequences of prolonged wakefulness are unknown. The stimulant modafinil may promote primarily dopaminergic neurotransmission. Catechol-O-methyltransferase (COMT) catalyzes the breakdown of cerebral dopamine. A functional Val158Met polymorphism reduces COMT activity, and Val/Val homozygous individuals presumably have lower dopaminergic signaling in the prefrontal cortex than do Met/Met homozygotes. We quantified the contribution of this polymorphism to the effects of sleep deprivation and modafinil on subjective state, cognitive performance, and recovery sleep in healthy volunteers. Two-time 100 mg modafinil potently improved vigor and well-being, and maintained baseline performance with respect to executive functioning and vigilant attention throughout sleep deprivation in Val/Val genotype subjects but was hardly effective in subjects with the Met/Met genotype. Neither modafinil nor the Val158Met polymorphism affected distinct markers of sleep homeostasis in recovery sleep. In conclusion, dopaminergic mechanisms contribute to impaired waking functions after sleep loss.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Pharmacology and Toxicology|
04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Medical Molecular Genetics
04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||18 Dec 2008 12:14|
|Last Modified:||23 Nov 2012 14:08|
|Publisher:||Nature Publishing Group|
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