Atomoxetine Modulates Right Inferior Frontal Activation During Inhibitory Control: A Pharmacological Functional Magnetic Resonance Imaging Study

Background Atomoxetine, a selective noradrenaline reuptake inhibitor (SNRI) licensed for the treatment of attention-deficit/hyperactivity disorder (ADHD), has been shown to improve response inhibition in animals, healthy volunteers, and adult patients. However, the mechanisms by which atomoxetine im...

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Bibliographic Details
Published in:Biological psychiatry (1969) 2009-04, Vol.65 (7), p.550-555
Main Authors: Chamberlain, Samuel R, Hampshire, Adam, Müller, Ulrich, Rubia, Katya, del Campo, Natalia, Craig, Kevin, Regenthal, Ralf, Suckling, John, Roiser, Jonathan P, Grant, Jon E, Bullmore, Edward T, Robbins, Trevor W, Sahakian, Barbara J
Format: Article
Language:English
Subjects:
Adrenergic Uptake Inhibitors - blood
Adrenergic Uptake Inhibitors - pharmacology
Adult
Atomoxetine
Atomoxetine Hydrochloride
Biological and medical sciences
cognition
Double-Blind Method
fMRI
Frontal Lobe - drug effects
Humans
impulsiveness
impulsivity
inhibition
Inhibition (Psychology)
Magnetic Resonance Imaging
Male
Medical sciences
Middle Aged
neuromodulation
noradrenaline
Placebos
Propylamines - blood
Propylamines - pharmacology
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Reaction Time - drug effects
SSRT
stop-signal
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Summary:Background Atomoxetine, a selective noradrenaline reuptake inhibitor (SNRI) licensed for the treatment of attention-deficit/hyperactivity disorder (ADHD), has been shown to improve response inhibition in animals, healthy volunteers, and adult patients. However, the mechanisms by which atomoxetine improves inhibitory control have yet to be determined. Methods The effects of atomoxetine (40 mg) were measured with a stop-signal functional magnetic resonance imaging (fMRI) paradigm in 19 healthy volunteers, in a within-subject, double-blind, placebo-controlled design. Results Atomoxetine improved inhibitory control and increased activation in the right inferior frontal gyrus when volunteers attempted to inhibit their responses (irrespective of success). Plasma levels of drug correlated significantly with right inferior frontal gyrus activation only during successful inhibition. Conclusions These results show that atomoxetine exerts its beneficial effects on inhibitory control via modulation of right inferior frontal function, with implications for understanding and treating inhibitory dysfunction of ADHD and other disorders.
ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2008.10.014