Einfluss des Dopamin-1 Rezeptor-Subtyps auf inhibitorische Neuroplastizität am Modell des motorischen Kortex des Menschen
Exploration of D1-receptor impact on inhibitory neuroplasticity on the model of the human motor cortex
von Jan Christian Alexander Grosch
Datum der mündl. Prüfung:2017-05-30
Erschienen:2017-05-22
Betreuer:Prof. Dr. Michael Nitsche
Gutachter:Prof. Dr. Michael Müller
Gutachter:Prof. Dr. Martin Oppermann
Dateien
Name:Doktorarbeit Grosch Final mit Tag.pdf
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Format:PDF
Zusammenfassung
Englisch
The neuromodulator Dopamine improves in both animal and human experiments learning and memory formation. The proposed mechanism behind the positive effects of Dopamine on cognition is a focusing effect on neuroplasticity. In humans, L-dopa prolonged focal facilitatory and nonfocal inhibitory plasticity, but turned nonfocal facilitatory plasticity into inhibition, thus demonstrating a focusing effect on neuroplasticity. Here we analyze the impact of D1 receptors on focal and nonfocal inhibitory neuroplasticity by comparing the effects of a relative and a complete activation of D1-receptors on focal and nonfocal inhibitory neuroplasticity with placebo medication in a group of healthy subjects. Focal plasticity was induced by paired associative stimulation (PAS10) and nonfocal plasticity by transcranial direct current stimulation (cathodal tDCS). Relative enhancement of D1-receptors was achieved by administering the D2-antagonist Sulpiride and complete activation by a combination of 100 mg L-dopa and Sulpiride. Under placebo PAS10 and cathodal tDCS reduced motorcortex excitability. Sulpiride abolished PAS10-induced inhibition. In an earlier study Sulpiride abolished tDCS-induced inhibitory plasticity. Combining Sulpiride with L-dopa reestablished both PAS10- and tDCS-induced inhibition but lacked any consolidating effects. These results show that a sufficient level of D1-receptor activity sustains the formation of both focal and nonfocal inhibitory neuroplasticity. However, an appropriate balance of D1 and D2 activity seems necessary to achieve the focusing and consolidating effect of Dopamine on neuroplasticity.
Keywords: Neuroplasticity; Dopamine; D1-receptor; tDCS; PAS