Behavioural impact of a double dopaminergic and serotonergic lesion in the non-human primate

Brain. 2015 Sep;138(Pt 9):2632-47. doi: 10.1093/brain/awv183. Epub 2015 Jun 27.


Serotonergic (5-HT) neurons degenerate in Parkinson's disease. To determine the role of this 5-HT injury-besides the dopaminergic one in the parkinsonian symptomatology-we developed a new monkey model exhibiting a double dopaminergic/serotonergic lesion by sequentially using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3,4-methylenedioxy-N-methamphetamine (MDMA, better known as ecstasy). By positron emission tomography imaging and immunohistochemistry, we demonstrated that MDMA injured 5-HT nerve terminals in the brain of MPTP monkeys. Unexpectedly, this injury had no impact on tremor or on bradykinesia, but altered rigidity. It abolished the l-DOPA-induced dyskinesia and neuropsychiatric-like behaviours, without altering the anti-parkinsonian response. These data demonstrate that 5-HT fibres play a critical role in the expression of both motor and non-motor symptoms in Parkinson's disease, and highlight that an imbalance between the 5-HT and dopaminergic innervating systems is involved in specific basal ganglia territories for different symptoms.

Keywords: Parkinson’s disease; dyskinesia; monkey; neuropsychiatric symptoms; serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds
  • Animals
  • Antiparkinson Agents / therapeutic use
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain Mapping
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Dopamine Agents / toxicity
  • Female
  • Levodopa / therapeutic use
  • MPTP Poisoning / chemically induced
  • MPTP Poisoning / drug therapy
  • MPTP Poisoning / physiopathology*
  • Macaca fascicularis
  • Male
  • Mental Disorders / etiology*
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity
  • Nortropanes
  • Radionuclide Imaging
  • Serotonin / metabolism*
  • Serotonin Agents / toxicity
  • Sulfides


  • 3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile
  • Aniline Compounds
  • Antiparkinson Agents
  • Dopamine Agents
  • N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane
  • Nortropanes
  • Serotonin Agents
  • Sulfides
  • Serotonin
  • Levodopa
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Dopamine