D1-Receptor Impact on Neuroplasticity in Humans

Dopamine improves learning and memory formation. The neurophysiological basis for these effects might be a focusing effect of dopamine on neuroplasticity: Accordingly, in humans L-dopa prolongs focal facilitatory plasticity, but turns nonfocal facilitatory plasticity into inhibition. Here we explore the impact of D-1 receptors on plasticity. Nonfocal plasticity was induced by transcranial direct current stimulation (tDCS), and focal plasticity by paired associative stimulation (PAS). Subjects received sulpiride, a D-2 antagonist, to increase the relative contribution of D-1 receptors to dopaminergic activity, combined sulpiride and L-dopa, to increase the relation of D-1/D-2 activity further, or placebo medication. Under placebo, anodal tDCS and excitatory PAS(ePAS) increased motor cortex excitability. Cathodal tDCS and inhibitory PAS (iPAS) reduced it. Sulpiride abolished iPAS-induced inhibition, but not ePAS-generated facilitation, underlining the importance of D-1-receptor activity for focal facilitatory neuroplasticity. Combining sulpiride with L-dopa reestablished iPAS-induced inhibition, but did not affect ePAS-induced plasticity. tDCS-induced plasticity, which was abolished by sulpiride in a former study, also recovered. Thus enhancing D-1 activity further relative to D-2 activity is relevant for facilitatory and inhibitory plasticity. However, comparison with former results show that an appropriate balance of D-1 and D-2 activity seems necessary to (1) consolidate the respective excitability modifications and (2) to elicit a focusing effect.