Catecholaminergic consolidation of motor cortical neuroplasticity in humans.
Amphetamine, a catecholaminergic re-uptake-blocker, is 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 on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.
Nitsche
Michael A
MA
Department of Clinical Neurophysiology, Georg-August-University, Robert Koch Str. 40, 37075 Goettingen, Germany. mnitsch1@gwdg.de
Grundey
Jessica
J
Liebetanz
David
D
Lang
Nicolas
N
Tergau
Frithjof
F
Paulus
Walter
W
D000328:Adult; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D002395:Catecholamines / Q000502:physiology*; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*
D002395:Catecholamines; D000661:Amphetamine