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 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.