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 D₁ 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 D₂ antagonist, to increase the relative contribution of D₁ receptors to dopaminergic activity, combined sulpiride and L-dopa, to increase the relation of D₁/D₂ activity further, or placebo medication. Under placebo, anodal tDCS and excitatoryPAS(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 D₁-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 D₁ activity further relative to D₂ activity is relevant for facilitatory and inhibitory plasticity. However, comparison with former results show that an appropriate balance of D₁ and D₂ activity seems necessary to (1) consolidate the respective excitability modifications and (2) to elicit a focusing effect. [ABSTRACT FROM AUTHOR]