The effect of dopamine D2-like receptor blockade on human motor performance and skill acquisition

TL;DR

Blocking dopamine D2-like receptors temporarily impairs motor skill learning in humans, but the effect fades over time.

Contribution

This study provides causal evidence linking dopamine D2-like receptor modulation to early motor skill acquisition in humans.

Findings

Sulpiride reduced motor performance during initial skill acquisition compared to placebo.

The performance difference disappeared during the retention test, suggesting no long-term consolidation deficit.

Sulpiride led to slower execution of the motor task relative to placebo.

Abstract

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-like receptor in the acquisition and consolidation stages of motor learning remains unclear. The aim of this study was to examine the effect of a selective D2-like receptor antagonist on human motor skill acquisition and consolidation. 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 (800 mg) or placebo. A 20-minute bout of high-intensity interval cycling exercise was included to enhance learning effects and counteract potentially confounding sedative effects of sulpiride. Results showed that 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. Our results provide preliminary evidence of a causal relationship between neuromodulation at the dopamine D2-like receptor and motor performance during 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 acquisition and slow subsequent performance of the skill.

The online version contains supplementary material available at 10.1038/s41598-026-36241-7.

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