MODULATION OF [H-3] MAZINDOL BINDING-SITES IN RAT STRIATUM BY DOPAMINERGIC AGENTS

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 [H-3]mazindoI 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 [H-3]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.