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. (C) 2002 Elsevier Science B.V. All rights reserved.