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Psychostimulant effect of levodopa: reversing sensitisation is possible
  1. Anna Castrioto1,2,3,
  2. Andrea Kistner1,2,
  3. Hélène Klinger4,5,
  4. Eugénie Lhommée1,2,
  5. Emmanuelle Schmitt1,2,
  6. Valérie Fraix1,2,
  7. Stephan Chabardès6,2,
  8. Patrick Mertens7,
  9. Jean-Louis Quesada8,
  10. Emmanuel Broussolle4,5,
  11. Pierre Pollak1,2,9,
  12. Stéphane C Thobois4,5,
  13. Paul Krack1,2
  1. 1Movement Disorder Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Joseph Fourier University, Grenoble, France
  2. 2INSERM, Unité 836, Grenoble Institut des Neurosciences, Grenoble, France
  3. 3Clinica Neurologica, Università degli Studi di Perugia, Perugia, Italy
  4. 4Service de Neurologie C, Université Lyon I, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Lyon, France
  5. 5CNRS, UMR 5229, Centre de Neurosciences Cognitives, Lyon, France
  6. 6Neurosurgery Department, CHU de Grenoble, Joseph Fourier University, Grenoble, France
  7. 7Service de Neurochirurgie A, Université Lyon I, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Lyon, France
  8. 8Centre d'Investigation Clinique CHU de Grenoble, UJF-Grenoble 1/CNRS, TIMC-IMAG UMR 5525, Grenoble, France
  9. 9Hôpitaux Universitaires de Genève, Service de Neurologie, Genève, Switzerland
  1. Correspondence to Dr A Castrioto, Movement Disorder Unit, Pavillon de Neurologie, CHU Grenoble, Joseph Fourier University, Cedex 9, Grenoble 38043, France; acastrioto{at}chu-grenoble.fr

Abstract

Background Levodopa therapy in Parkinson's 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.

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