Characterization of both dopamine uptake systems in rat striatal slices byspecific pharmacological tools

Previous results have shown that modifications of dopamine (DA) high-affini ty uptake, and those of DA low-affinity uptake, in rat striatal slices were different after autoxidation of this model and in the presence of antioxid ants. The aim of this study was to determine whether these two DA uptake sy stems correspond to two different dopamine transporters or rather to a sing le one. A lesion into the substantia nigra of animals by injection of 6-hyd roxydopamine, a neurotoxic substance of nigrostriatal dopaminergic neurons led to the suppression of both DA uptake systems. These two DA uptake syste ms were not modified when animals were treated by reserpine or tetrabenazin e, which inhibit the vesicular monoamine transporter. Moreover, they were s odium- and temperature-dependent. Experiments with specific inhibitors show ed that 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)-piperazine dihydro chloride (GBR-12935) and (E)-N-(3-iodoprop-2-enyl)-2 beta-carbomethoxy-3 be ta-(4'-tolyl) nortropane chloride (PE2I), two selective DA uptake inhibitor s, were significantly more potent than fluoxetine and nisoxetine (selective serotonin and norepinephrine uptake inhibitors respectively) in both DA up take systems. However, the concentrations of these products inhibiting low- affinity uptake, by 50% were much greater than those for high-affinity upta ke,. Our data indicate that both DA uptake systems are neuronal, independent of the vesicular monoamine transporter, active and specific for dopamine. Our results suggest that high-affinity uptake, and low-affinity uptake, corresp ond to the same dopamine transporter, but would be situated at different le vels in the striatal slice model. Uptake, could take place at the periphery of the slice whereas uptake, in the depth of the slice. (C) 1998 Elsevier Science Ltd. All rights reserved.