Dose-Dependent Inverted U-Shaped Effect of Dopamine (D-2-Like) Receptor Activation on Focal and Nonfocal Plasticity in Humans

Abstract

The neuromodulator dopamine (DA) has multiple modes of action on neuroplasticity induction and modulation, depending on subreceptor specificity, concentration level, and the kind of stimulation-induced plasticity. To determine the dosage-dependent effects of D-2-like receptor activation on nonfocal and focal neuroplasticity in the human motor cortex, different doses of ropinirole (0.125, 0.25, 0.5, and 1.0 mg), a D-2/D-3 dopamine agonist, or placebo medication were combined with anodal and cathodal transcranial direct current stimulation (tDCS) protocols, which induce nonfocal plasticity, or paired associative stimulation (PAS, ISI of 10 or 25 ms), which generates focal plasticity, in healthy volunteers. D-2-like receptor activation produced an inverted "U"-shaped dose-response curve on plasticity for facilitatory tDCS and PAS and for inhibitory tDCS. Here, high or low dosages of ropinirole impaired plasticity. However, no dose-dependent response effect of D-2-like receptor activation was evident for focal inhibitory plasticity. In general, our study supports the assumption that modulation of D-2-like receptor activity exerts dose-dependent inhibitory or facilitatory effects on neuroplasticity in the human motor cortex depending on the topographic specificity of plasticity.