Connectome and molecular pharmacological dopaminergic differences in RLS: plastic changes and neuroadaptations that may contribute to augmentation

• Long-term treatment of RLS dopamine D2/D3 receptor agonists leads to augmentation• Augmentation may be a consequence of a hyper-dopaminergic state• Protein tyrosine phosphatase D (PTPRD) may play a role in the reconfiguration of neural circuits• Alterations in direct and indirect interactions between D1 and D3 receptors might be involved• New treatment options for RLS may reach beyond the dopamine system itself

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