¹Department of Experimental Psychology, Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, UK

Correspondence: Dr DM Eagle, Department of Experimental Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Downing Street, Cambridge CB2 3EB, UK. Tel: +44 1223 765 292; Fax: +44 1223 333 564; E-mail: de102@cam.ac.uk

²Current address: Department of Pharmacology, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK.

Received 26 January 2007; Revised 23 April 2007; Accepted 17 May 2007; Published online 18 July 2007.

Abstract

Atomoxetine is a noradrenaline-specific reuptake inhibitor used clinically for the treatment of childhood and adult attention deficit hyperactivity disorder (ADHD). Studies in human volunteers and patient groups have shown that atomoxetine improves stop-signal reaction time (SSRT) performance, an effect consistent with a reduction in motor impulsivity. However, ADHD is a heterogeneous disorder and it is of interest to determine whether atomoxetine is similarly effective against other forms of impulsivity, as well as the attentional impairment present in certain subtypes of ADHD. The present study examined the effects of atomoxetine on impulsivity using an analogous SSRT task in rats and two additional tests of impulsivity; delay discounting of reward and the five-choice serial reaction time task (5CSRTT), the latter providing an added assessment of sustained visual attention. Atomoxetine produced a significant dose-dependent speeding of SSRT. In addition, atomoxetine produced a selective, dose-dependent decrease in premature responding on the 5CSRTT. Finally, on the delay-discounting task, atomoxetine significantly decreased impulsivity by increasing preference for the large-value reward across increasing delay. These findings conclusively demonstrate that atomoxetine decreases several distinct forms of impulsivity in rats. The apparent contrast of these effects with stimulant drugs such as amphetamine and methylphenidate, which generally act to increase impulsivity on the 5CSRTT, may provide new insights into the mechanisms of action of stimulant and nonstimulant drugs in ADHD.