Dopamine reuptake inhibition and failure to evoke dyskinesia in MPTP-treated primates

Eur J Pharmacol. 2002 Sep 13;451(2):157-60. doi: 10.1016/s0014-2999(02)02268-9.

Abstract

Nonspecific monoamine reuptake inhibitors reverse motor abnormalities in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets without evoking established dyskinesia. However, it is not known whether dopamine reuptake inhibition alone explains these actions or whether noradrenaline and/or serotonin reuptake blockade also contributes. L-DOPA (12.5 mg/kg, p.o.) rapidly reversed the baseline locomotor deficits and motor disabilities, but evoked dyskinesia (especially limb chorea) in MPTP-treated common marmosets primed to exhibit involuntary movements. In contrast, the selective dopamine reuptake inhibitor 1-(2-(bis-(4-fluorophenyl)-methoxy)ethyl)-4-(3-phenylpropyl) piperazine dihydrochloride (GBR 12909) reversed motor deficits in a dose-dependent manner but, unlike L-DOPA, did not evoke established dyskinesia in these animals. Therefore, inhibition of dopamine reuptake does not evoke established dyskinesia in MPTP-treated primates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Animals
  • Callithrix
  • Dopamine Uptake Inhibitors / pharmacology*
  • Dopamine Uptake Inhibitors / therapeutic use
  • Dose-Response Relationship, Drug
  • Dyskinesia, Drug-Induced* / prevention & control
  • Levodopa / toxicity
  • Motor Activity / drug effects
  • Motor Activity / physiology

Substances

  • Dopamine Uptake Inhibitors
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine