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Dopaminergic impact on neuroplasticity in humans: the importance of balance
Objective: Dopamine is involved in cognitive mechanisms. In humans and animals, dopamine improves learning and memory formation. The neurophysiological foundation for this beneficial effect might be a focusing effect of dopamine, and thus an improvement of neuroplasticity, as shown in animal experiments. Knowledge about the effects of dopamine on neuroplasticity in humans is scarce. In line with the focusing hypothesis medication with l-dopa consolidates focal, excitability-enhancing plasticity in humans, while suppressing non-focal excitability-enhancing and strengthening inhibitory plasticity. D2-agonism only stabilised inhibitory plasticity. Here we aim to explore the impact of the D1 receptor on plasticity.
Methods: Six to twelve healthy subjects were studied in the respective experiments. The primary motor cortex was taken as a model. Transcranial direct current stimulation (tDCS, current density 0.286 mA/cm2, 9min cathodal, 13min anodal tDCS) was applied to induce non-focal plasticity, paired associative stimulation (PAS, interstimulus interval 25 and 10ms) to induce focal plasticity. Motor evoked potentials (MEPs) were recorded to monitor cortical excitability. Subjects received 400mg sulpiride, a combination of 400mg sulpiride and 100mg l-dopa or placebo medication before the plasticity-inducing procedures.
Results: Under placebo medication, anodal tDCS and PAS25 induced motor cortex excitability enhancements for about 30min. Cathodal tDCS and PAS10 resulted in reversed after-effects. Sulpiride abolished the tDCS- and PAS10-effects on excitability, but did not affect the excitability enhancement accomplished by PAS25. Combination of sulpiride with l-dopa re-established the excitability enhancement produced by anodal tDCS and PAS 25, and moreover prolonged the effects of PAS25 for up to 90min after stimulation. Additionally, it re-established the inhibitory effects of cathodal tDCS and PAS10.
Conclusions: D1 receptor activity is important for the induction of focal excitability-enhancing neuroplasticity. Enhancing D1 activity further relative to D2 activity has also positive effects on non-focal excitability enhancing plasticity and on excitability-diminishing plasticity. However, an appropriate balance of D1 and D2 activity seems neccessary to (a) consolidate the respective excitability modifications and (b) to elicit a focusing dopaminergic effect, because the latter were only accomplished by simultaneous D1 and D2 activation by l-dopa.