ORIGINAL INVESTIGATION Effect of D-amphetamine on inhibition and motor planning as a function of baseline performance Ava-Ann Allman & Chawki Benkelfat & France Durand & Igor Sibon & Alain Dagher & Marco Leyton & Glen B. Baker & Gillian A. O’Driscoll Received: 22 April 2010 / Accepted: 4 June 2010 / Published online: 4 July 2010 # Springer-Verlag 2010 Abstract Rationale Baseline performance has been reported to predict dopamine (DA) effects on working memory, following an inverted-U pattern. This pattern may hold true for other executive functions that are DA-sensitive. Objectives The objective of this study is to investigate the effect of D-amphetamine, an indirect DA agonist, on two other putatively DA-sensitive executive functions, inhibi- tion and motor planning, as a function of baseline performance. Methods Participants with no prior stimulant exposure participated in a double-blind crossover study of a single dose of 0.3 mg/kg, p.o. of D-amphetamine and placebo. Participants were divided into high and low groups, based on their performance on the antisaccade and predictive saccade tasks on the baseline day. Executive functions, mood states, heart rate and blood pressure were assessed before (T0) and after drug administration, at 1.5 (T1), 2.5 (T2) and 3.5 h (T3) post-drug. Results Antisaccade errors decreased with D-amphetamine irrespective of baseline performance (p =0.025). For anti- saccade latency, participants who generated short-latency antisaccades at baseline had longer latencies on D-amphet- amine than placebo, while those with long-latency antisac- cades at baseline had shorter latencies on D-amphetamine than placebo (drug×group, p =0.04). D-amphetamine did not affect motor planning. Ratings of mood improved on D- amphetamine (p <0.001). Magnitude of D-amphetamine- induced changes in elation was related to baseline reaction time variability. Conclusions D-amphetamine reduced antisaccade error rates in healthy controls, replicating and extending findings with DA agonists in clinical populations. D-amphetamine had baseline-dependent effects on antisaccade latency, consistent with an inverted-U relationship between perfor- mance and DA activity. Keywords Motor planning . Inhibition . D-amphetamine . Eye movements . Dopamine Introduction Executive functions are higher-order cognitive processes that bring behaviour under strategic or volitional control (Logan 2004). Examples include working memory, or the maintenance and manipulation of information over a short period of time (Baddeley 1992), response inhibition, or the A.-A. Allman : M. Leyton : G. A. O’Driscoll (*) Department of Psychology, McGill University, 1205 Dr. Penfield Avenue, Montreal, QC H3A 1B1, Canada e-mail: gillian@hebb.psych.mcgill.ca C. Benkelfat : F. Durand : I. Sibon : M. Leyton : G. A. O’Driscoll Department of Psychiatry, McGill University, Montreal, QC, Canada C. Benkelfat : A. Dagher : M. Leyton Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada G. A. O’Driscoll Douglas Hospital Research Center, Verdun, QC, Canada C. Benkelfat : A. Dagher : M. Leyton : G. A. O’Driscoll McConnell Brain Imaging Centre, McGill University, Montreal, QC, Canada G. B. Baker Department of Psychiatry, Mackenzie Centre, University of Alberta, Edmonton, AB, Canada Psychopharmacology (2010) 211:423–433 DOI 10.1007/s00213-010-1912-x