Abstract Rationale: Dopamine signalling supports motor skill learning in a variety of ways, including through an effect on cortical and striatal plasticity. One neuromodulator that has been consistently linked to motor skill learning is dopamine. However, the specific role of dopamine D2 receptor in the acquisition and consolidation stages of motor learning remains unclear. Objectives To examine the effect of a selective D2 receptor antagonist on human motor skill acquisition and consolidation. Methods In this randomised, double-blind, placebo-controlled design, healthy adult men and women (N = 23) completed a sequential motor skill learning task after taking either sulpiride (800mg) or placebo. A 20-minute bout of high-intensity interval cycling exercise was included to enhance experimental effects and counteract potentially confounding sedative effects of sulpiride. Results Sulpiride reduced performance during motor skill acquisition relative to placebo in the first session, however this difference was abolished at the subsequent retention test. Sulpiride did not reduce consolidation of learning as expected, however it led to a reduction in speed of execution relative to placebo. Conclusions Our results demonstrate that neuromodulation at the dopamine D2 receptor is critical in the early acquisition of a novel motor skill. These results may have functional relevance in motor rehabilitation as reduced dopamine transmission can impact performance during initial learning and slow subsequent performance of the skill.

The effect of dopamine D2 receptor blockade on human motor skill learning