Effect of d-amphetamine on inhibition and motor planning as a function of baseline performance

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. 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, inhibition and motor planning, as a function of baseline performance. 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. Antisaccade errors decreased with d-amphetamine irrespective of baseline performance (p = 0.025). For antisaccade latency, participants who generated short-latency antisaccades at baseline had longer latencies on d-amphetamine than placebo, while those with long-latency antisaccades at baseline had shorter latencies on d-amphetamine than placebo (drug x 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. 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 performance and DA activity.