title: D1-receptor impact on neuroplasticity in humans.
abstract: 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.
authors.affiliation: Department of Clinical Neurophysiology, Georg August University, 37099 Göttingen, Germany. mnitsch1@gwdg.de
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nitsche
authors.forename: Min-Fang
authors.initials: MF
authors.lastname: Kuo
authors.forename: Jan
authors.initials: J
authors.lastname: Grosch
authors.forename: Christin
authors.initials: C
authors.lastname: Bergner
authors.forename: Katia
authors.initials: K
authors.lastname: Monte-Silva
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015259:Dopamine Agents / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D055815:Young Adult
chemical_list: D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D007980:Levodopa; D013469:Sulpiride