Dopamine reuptake inhibition and failure to evoke dyskinesia in MPTP-treated primates.
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.
Hansard
Matthew J
MJ
Neurodegenerative Disease Research Centre, Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College, London SE1 1UL, UK.
Smith
Lance A
LA
Jackson
Michael J
MJ
Cheetham
Sharon C
SC
Jenner
Peter
P
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002144:Callithrix; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control; D007980:Levodopa / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology
D018765:Dopamine Uptake Inhibitors; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine