title: Psychostimulant effect of levodopa: reversing sensitisation is possible.
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.
authors.affiliation: Movement Disorder Unit, Pavillon de Neurologie, CHU Grenoble, Joseph Fourier University, Cedex 9, Grenoble 38043, France. acastrioto@chu-grenoble.fr
authors.forename: Anna
authors.initials: A
authors.lastname: Castrioto
authors.forename: Andrea
authors.initials: A
authors.lastname: Kistner
authors.forename: Hélène
authors.initials: H
authors.lastname: Klinger
authors.forename: Eugénie
authors.initials: E
authors.lastname: Lhommée
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Schmitt
authors.forename: Valérie
authors.initials: V
authors.lastname: Fraix
authors.forename: Stephan
authors.initials: S
authors.lastname: Chabardès
authors.forename: Patrick
authors.initials: P
authors.lastname: Mertens
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Quesada
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Broussolle
authors.forename: Pierre
authors.initials: P
authors.lastname: Pollak
authors.forename: Stéphane C
authors.initials: SC
authors.lastname: Thobois
authors.forename: Paul
authors.initials: P
authors.lastname: Krack
mesh_terms: D001007:Anxiety / Q000139:chemically induced / Q000150:complications; D001479:Basal Ganglia / Q000187:drug effects; D046690:Deep Brain Stimulation / Q000379:methods / Q000523:psychology*; D003863:Depression / Q000139:chemically induced / Q000150:complications; D018491:Dopamine Agonists / Q000009:adverse effects* / Q000627:therapeutic use; D004409:Dyskinesia, Drug-Induced / Q000150:complications / Q000628:therapy*; D005059:Euphoria / Q000187:drug effects*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000187:drug effects; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000628:therapy*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D020531:Subthalamic Nucleus / Q000502:physiology
chemical_list: D018491:Dopamine Agonists; D007980:Levodopa