Pharmacological Consolidation of Motor Cortical Neuroplasticity in Humans

Introduction: Amphetamine, a catecholaminergic re-uptake blocker, and D-cycloserine, a partial NMDA receptor-agonist, are able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here we study the impact of amphetamine and D-cycloserine on NMDA receptor-dependent excitability modifications in the human motor cortex elicited by weak transcranial direct-current stimulation (tDCS). Methods: tDCS protocols which elicit long-lasting motor cortical excitability modifications were applied under premedication with 20mg amfetaminil (AMP), 100mg D-cycloserine (CYC) or placebo medication. For the excitability-enhancing anodal tDCS a premedication of 20mg AMP and 150mg dextromethorphan, an NMDA receptor-antagonist, was administered in a control experiment. Motor cortex excitability was monitored by single pulse transcranial magnetic stimulation. Results: AMP and CYC significantly enhanced and prolonged increases in anodal, tDCS-elicited, long-lasting motor cortical excitability. Under AMP and CYC premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to about 1h in the placebo condition. The additional administration of the NMDA receptor-antagonist dextrometorphan blocked any enhancement of tDCS-driven excitability under AMP. Conclusions: In this study, low-dosage AMP as well as CYC administration consolidated tDCS-induced neuroplastic effects, but did not initiate them. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.