Modulation kognitiver Funktionen durch die Einnahme einer Einmaldosis des Noradrenalin-Wiederaufnahmehemmers Atomoxetin bei gesunden freiwilligen Probanden: eine randomisierte, placebo-kontrollierte Studie mittels funktioneller Magnetresonanztomographie
LicenseStandard (Fassung vom 01.10.2008)
Atomoxetine (ATMX) is a norepinephrine reuptake inhibitor approved for the treatment of ADHD with its core symptoms hyperactivity, inattention and impulsivity. In healthy controls it has been shown that ATMX improves inhibitory control by enhancing prefrontal cortex functioning. However, since inhibitory control will never be perfect, we investigated the drug-effects on the error-monitoring system which is activated when inhibitory control fails. 12 healthy male subjects with hepatic CYP450-2D6-EM status were included. We used a double-blind placebo-controlled within-subject design to examine the effects of 80mg ATMX on neural responses during an fMRI-GoNoGo-Flanker paradigm. Besides neuropsychological tests, self-rating scales and monitoring of cardiovascular functions were applied to control for side effects that might bias interpretation of treatment effects. Pharmacokinetically, we observed an acclerated decline of ATMX serum levels over time. Mean heart rates increased after intake of ATMX. Controlling this cardiovascular effect on MR-based brain perfusion, measurements did not show significant effects. Behaviorally, ATMX led to an increase of trials in which inhibitory control failed. Functionally, ATMX attenuated neural error signals in regions described to error monitoring (IFC/ACC/pre-SMA). Further analyses revealed that this increase in error signals was not dependent on increased error rates, but reflects pure drug effects. Neuropsychological data indexed an increase in phasic alertness. A single-dose of 80mg ATMX resulted in accelerated pharmakokinetics and led to higher heart rates without altering brain perfusion. We observed attenuated neural error signals in relevant brain structures, in combination with increased rate of commission errors. Within the framework of a relationship between performance and arousal (Yerkes-Dodson law) present data are interpreted in terms of a shifted optimal working point of the norepinephrine system in healthy controls.
Subject HeadingsAtomoxetin [GND]
Funktionelle NMR-Tomographie [GND]
Attention deficit disorder with hyperactivity [MeSH]