This study was undertaken to examine whether repeated alteration of dopamine turnover influences the function of dopamine uptake sites. In the first experiment, rats were repeatedly injected intraperitoneally with L-3,4-dihydroxyphenylalanine (L-DOPA), alpha-methyl-p-tyrosine or 1-[2-bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine (GBR 12909) once daily for 14 days. An increase in the number of [3H]mazindol binding sites in the striatum was seen with L-DOPA and GBR 12909. A decrease was seen with alpha-methyl-p-tyrosine. In the second experiment, the effect of a single treatment with the same drugs was investigated and no change in the number and affinity of [3H]mazindol binding sites was found. These results indicate that the number of dopamine uptake sites is modulated by persistent changes in dopamine turnover, and that repeated treatment with a selective dopamine uptake inhibitor, GBR 12909, increases their number.
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