Serotonergic neurons mediate ectopic release of dopamine induced by L-DOPA in a rat model of Parkinson's disease

Neurobiol Dis. 2010 Apr;38(1):136-43. doi: 10.1016/j.nbd.2010.01.012. Epub 2010 Jan 22.

Abstract

Benefit and motor side effects of l-DOPA in Parkinson's disease have been related to dopamine transmission in the striatum. However, the putative involvement of serotonergic neurons in the dopaminergic effects of l-DOPA suggests that the striatum is not a preferential target of l-DOPA. By using microdialysis in a rat model of Parkinson's disease, we found that l-DOPA (3-100 mg/kg) increased dopamine extracellular levels monitored simultaneously in four brain regions receiving serotonergic innervation: striatum, substantia nigra, hippocampus, prefrontal cortex. The increase was regionally similar at the lowest dose and 2-3 times stronger in the striatum at higher doses. Citalopram, a serotonin reuptake blocker, or the destruction of serotonergic fibers by 5,7-dihydroxytryptamine impaired l-DOPA-induced dopamine release in all regions. These data demonstrate that l-DOPA induces an ectopic release of dopamine due to serotonergic neurons. The new pattern of dopamine transmission created by l-DOPA may contribute to the benefit and side effects of l-DOPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • Animals
  • Antiparkinson Agents / pharmacology
  • Brain / cytology
  • Brain / drug effects
  • Brain / metabolism
  • Citalopram / pharmacology
  • Cobra Neurotoxin Proteins / pharmacology
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Extracellular Fluid / drug effects
  • Extracellular Fluid / metabolism
  • Levodopa / pharmacology*
  • Male
  • Microdialysis
  • Oxidopamine
  • Parkinsonian Disorders / drug therapy*
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / physiopathology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Raphe Nuclei / drug effects*
  • Raphe Nuclei / metabolism
  • Rats
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / pharmacology
  • Sympatholytics
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Antiparkinson Agents
  • Cobra Neurotoxin Proteins
  • Serotonin Uptake Inhibitors
  • Sympatholytics
  • neurotoxin 12-1
  • Citalopram
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • Levodopa
  • Oxidopamine
  • Dopamine