Exercise is known to benefit motor skill learning in health and neurological disease. Evidence from brain stimulation, genotyping, and Parkinson's disease studies converge to suggest that the dopamine D2 receptor, and shifts in the cortical excitation and inhibition (E:I) balance, are prime candidates for the drivers of exercise-enhanced motor learning. However, causal evidence using experimental pharmacological challenge is lacking. We hypothesized that the modulatory effect of the dopamine D2 receptor on exercise-induced changes in the E:I balance would determine the magnitude of motor skill acquisition. To test this, we measured exercise-induced changes in excitation and inhibition using paired-pulse transcranial magnetic stimulation (TMS) in 22 healthy female and male humans, and then had participants learn a novel motor skill—the sequential visual isometric pinch task (SVIPT). We examined the effect of D2 receptor blockade (800 mg sulpiride) on these measures within a randomized, double-blind, placebo-controlled design. Our key result was that motor skill acquisition was driven by an interaction between the D2 receptor and E:I balance. Specifically, poorer skill learning was related to an attenuated shift in the E:I balance in the sulpiride condition, whereas this interaction was not evident in placebo. Our results demonstrate that exercise-primed motor skill acquisition is causally influenced by D2 receptor activity on motor cortical circuits.

众所周知，运动有利于健康和神经系统疾病的运动技能学习。来自大脑刺激、基因分型和帕金森病研究的证据一致表明，多巴胺 D2 受体以及皮质兴奋和抑制 (E:I) 平衡的变化是运动增强运动学习驱动因素的主要候选者。然而，缺乏使用实验药理学挑战的因果证据。我们假设多巴胺 D2 受体对运动引起的 E:I 平衡变化的调节作用将决定运动技能习得的程度。为了测试这一点，我们使用配对脉冲经颅磁刺激 (TMS) 对 22 名健康女性和男性进行了运动引起的兴奋和抑制变化的测量，然后让参与者学习一种新颖的运动技能——顺序视觉等长收缩任务 (SVIPT) ）。我们在随机、双盲、安慰剂对照设计中检查了 D2 受体阻断剂（800 毫克舒必利）对这些措施的影响。我们的主要结果是，运动技能的获得是由 D2 受体和 E:I 平衡之间的相互作用驱动的。具体来说，较差的技能学习与舒必利条件下 E:I 平衡的减弱有关，而这种相互作用在安慰剂中并不明显。我们的结果表明，运动引发的运动技能习得受到运动皮层回路上 D2 受体活性的因果影响。