Department of Clinical Neurophysiology, Georg August University, D-37075 Göttingen, Germany.
Department of Clinical Neurophysiology, Georg August University, D-37075 Göttingen, Germany
J Neurosci. 2014 Aug 6;34(32):10701-9. doi: 10.1523/JNEUROSCI.0832-14.2014.
The neuromodulator dopamine plays an important role in synaptic plasticity. The effects depend on receptor subtypes, affinity, concentration level, and the kind of neuroplasticity induced. In animal experiments, dopamine D2-like receptor stimulation revealed partially antagonistic effects on plasticity, which might be explained by dosage dependency. In humans, D2 receptor block abolishes plasticity, and the D2/D3, but predominantly D3, receptor agonist ropinirol has a dosage-dependent nonlinear affect on plasticity. Here we aimed to determine the specific affect of D2 receptor activation on neuroplasticity in humans, because physiological effects of D2 and D3 receptors might differ. Therefore, we combined application of the selective D2 receptor agonist bromocriptine (2.5, 10, and 20 mg or placebo medication) with anodal and cathodal transcranial direct current stimulation (tDCS), which induces nonfocal plasticity, and with paired associative stimulation (PAS) generating a more focal kind of plasticity in the motor cortex of healthy humans. Plasticity was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. For facilitatory tDCS, bromocriptine prevented plasticity induction independent from drug dosage. However, its application resulted in an inverted U-shaped dose-response curve on inhibitory tDCS, excitability-diminishing PAS, and to a minor degree on excitability-enhancing PAS. These data support the assumption that modulation of D2-like receptor activity exerts a nonlinear dose-dependent effect on neuroplasticity in the human motor cortex that differs from predominantly D3 receptor activation and that the kind of plasticity-induction procedure is relevant for its specific impact.
神经调质多巴胺在突触可塑性中发挥重要作用。其作用取决于受体亚型、亲和力、浓度水平和诱导的神经可塑性类型。在动物实验中，多巴胺 D2 样受体刺激显示出对可塑性的部分拮抗作用，这可以通过剂量依赖性来解释。在人类中，D2 受体阻断会消除可塑性，而 D2/D3，主要是 D3，受体激动剂罗匹尼罗对可塑性具有剂量依赖性的非线性影响。在这里，我们旨在确定 D2 受体激活对人类神经可塑性的具体影响，因为 D2 和 D3 受体的生理效应可能不同。因此，我们将选择性 D2 受体激动剂溴隐亭（2.5、10 和 20mg 或安慰剂）与阳极和阴极经颅直流电刺激（tDCS）联合应用，tDCS 诱导非焦点可塑性，与产生更聚焦类型的运动皮层配对关联刺激（PAS）联合应用。在健康人类的运动皮层中，通过经颅磁刺激诱导的运动诱发电位幅度来监测可塑性。对于促进性 tDCS，溴隐亭独立于药物剂量预防可塑性诱导。然而，其应用导致抑制性 tDCS、兴奋性降低的 PAS 以及在一定程度上兴奋性增强的 PAS 的倒 U 形剂量反应曲线。这些数据支持这样的假设，即 D2 样受体活性的调节对人类运动皮层的神经可塑性产生非线性剂量依赖性影响，与主要的 D3 受体激活不同，并且可塑性诱导程序对其特定影响是相关的。
