Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex

Introduction: Dopaminergic mechanisms participate in NMDA receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Therefore, transcranial direct current stimulation (tDCS) of the primary motor cortex was used to induce NMDA receptor-dependent excitability modulations.

Methods: According to standard protocols, 9min cathodal or 13min anodal tDCS, which are known to induce motor cortical excitability reductions or enhancements outlasting the stimulation for about one hour, were administered to 4–12 healthy humans in each experiment. tDCS-elicited excitability changes were monitored by single pulse transcranial magnetic stimulation (TMS) before and up to the day after tDCS. The dopaminergic influence on neuroplasticity was tested via application of 400mg sulpiride, a D2/D3 receptor antagonist, 0.025mg pergolide, a combined D1/D2 receptor agonist, or a combination of both drugs, which results in a selective D1 receptor activation. All experiments were conducted in a placebo medication-controlled, repeated measures design.

Results: D2 receptor block by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor block induced by co-administration of sulpiride and pergolide did not re-establish the excitability changes induced by tDCS. Enhancement of D2 Ð and to a lesser degree Ð of D1 receptors by pergolide consolidated tDCS-generated excitability diminution until the morning after stimulation.

Conclusions: The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the excitability-diminishing effects of cathodal tDCS for up to 24h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical excitability, e.g. migraine and epilepsy.