Reuptake of L-DOPA-derived extracellular DA in the striatum of a rodent model of Parkinson's disease via norepinephrine transporter

Synapse. 2008 Aug;62(8):632-5. doi: 10.1002/syn.20535.

Abstract

To determine the role of norepinephrine transporter in reuptake of L-DOPA-derived extracellular DA in the DA-denervated Parkinsonian striatum, we examined extracellular DA levels in the striatum of 6-hydroxyDA-lesioned rats that received L-DOPA (50 mg/kg with 12.5 mg/kg of benserazide) and L-DOPA plus desipramine (25 mg/kg), a selective norepinephrine reuptake inhibitor, using in vivo microdialysis. The pretreatment with desipramine increased levels of extracellular DA derived from administrated L-DOPA in the DA-denervated striatum. This study provides evidence that L-DOPA-derived DA is taken up by the norepinephrine transporter, instead of the dopamine transporter, in the striatum with dopaminergic denervation. This result suggests that the norepinephrine transporter could be a promising target in the treatment for Parkinson's disease.

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / pharmacology
  • Corpus Striatum / metabolism*
  • Corpus Striatum / physiopathology
  • Denervation
  • Desipramine / pharmacology
  • Disease Models, Animal
  • Dopamine / metabolism*
  • Extracellular Matrix / metabolism*
  • Levodopa / metabolism*
  • Levodopa / pharmacology
  • Male
  • Microdialysis
  • Neurons / metabolism
  • Norepinephrine / metabolism
  • Norepinephrine Plasma Membrane Transport Proteins / metabolism*
  • Oxidopamine
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / metabolism*
  • Parkinsonian Disorders / physiopathology
  • Rats
  • Rats, Wistar
  • Synapses / metabolism*
  • Synaptic Transmission / physiology

Substances

  • Antidepressive Agents, Tricyclic
  • Norepinephrine Plasma Membrane Transport Proteins
  • Levodopa
  • Oxidopamine
  • Desipramine
  • Dopamine
  • Norepinephrine