Psychostimulant effect of levodopa: reversing sensitisation is possible

Background Levodopa therapy in Parkinson9s disease (PD) is associated with non-motor complications resulting from sensitisation of the ventral striatum system. Recent studies showed an improvement in non-motor complications in PD patients with subthalamic stimulation. We hypothesised that ventral striatum desensitisation might contribute to this improvement. Methods Psychostimulant effects of levodopa were prospectively assessed in 36 PD patients with an acute levodopa challenge, before and 1 year after chronic subthalamic stimulation, using the Addiction Research Centre Inventory euphoria subscale. Postoperative evaluation was performed with the same dose of levodopa used in the preoperative assessment and after switching off stimulation. Preoperative and postoperative non-motor fluctuations in everyday life were investigated with the Ardouin Scale. Furthermore, in order to artificially reproduce non-motor fluctuations, a levodopa challenge keeping subthalamic stimulation on was performed to assess depression, anxiety and motivation before and after surgery under the different medication conditions. Results After 1 year of chronic subthalamic stimulation with 60.3% reduction in dopaminergic medication, the acute psychostimulant effects of levodopa were significantly reduced compared with preoperatively, as measured by the euphoria subscale (7.22±4.75 vs 4.75±5.68; p=0.0110). On chronic subthalamic stimulation and with markedly reduced dopaminergic medication, non-motor fluctuations were significantly improved. While off medication/on stimulation scores of depression and anxiety were improved, in the on medication/on stimulation condition the motivation score worsened. Conclusions Acute psychostimulant effects of levodopa (off stimulation) were significantly reduced 1 year after surgery. These findings are likely due to desensitisation of the ventral striatum, allowed by the reduction of dopaminergic treatment, and the replacement of pulsatile treatment with continuous subthalamic stimulation.