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.
Chamberlain
Samuel R
SR
Department of Psychiatry, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. srchamb@gmail.com
Hampshire
Adam
A
Müller
Ulrich
U
Rubia
Katya
K
Del Campo
Natalia
N
Craig
Kevin
K
Regenthal
Ralf
R
Suckling
John
J
Roiser
Jonathan P
JP
Grant
Jon E
JE
Bullmore
Edward T
ET
Robbins
Trevor W
TW
Sahakian
Barbara J
BJ
D018759:Adrenergic Uptake Inhibitors / Q000097:blood / Q000494:pharmacology*; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D004311:Double-Blind Method; D005625:Frontal Lobe / Q000187:drug effects*; D006801:Humans; D007266:Inhibition, Psychological; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011437:Propylamines / Q000097:blood / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D010919:Placebos; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride