These studies assess the distribution of [125I]RTI-55-labeled dopamine and serotonin uptake sites in the rat brain. Cocaine exerts its addictive properties through the blockade of DA uptake sites. Studies have been done to characterize the specific effects of cocaine on the brain, using ligands which bind at more than the DA uptake sites. Effort is being made to develop a ligand which is sensitive and specific for DA uptake sites. One of these ligands is [125I]RTI-55. We determined the distribution of these sites in the rat central nervous system in the present study. In addition, we evaluated the effects of 6-OHDA lesions in the nigrostriatal DA pathway. Unilateral lesions of the nigrostriatal dopaminergic pathway were performed by the stereotaxic application of 6- OHDA in the caudate-putamen. Sections were taken at the levels of the NAc, Cpu, and the substantia nigra pars compacta (SNpc). Autoradiographic distribution of total [125I]RTI-55 binding (no blocking agents) shows high binding densities in the Nac, the olfactory tubercle, the Cpu, and in the Snpc. Total binding shows a laminar distribution in the cortex. 6-OHDA caused marked decreases in [125I]RTI binding sites in the Nac and the Cpu. Sections incubated in the presence of paroxetine which blocks binding to 5-HT uptake sites caused a total disappearance of binding in the cortex. There were marked decreases in paroxetine-insensitive [125I]RTI binding sites in the Cpu and in the Snpc on the side of 6-OHDA lesions. Sections labeled with [125I]RTI in the presence of LR1111 which blocks binding of the ligand to dopamine uptake sites shows marked decreases in [125I]RTI55 binding in the Cpu. The laminar pattern of the distribution [125I]RTI in the cortex was still apparent even in the presence of LR111. There were small differences between the two sides of the brains of animals that had gotten 6-OHDA lesions. These results suggest that [125I]RTI55 binds to both striatal DA and 5-HT uptake sites. In the presence of paroxetine as a blocker, [125I]RTI may be a good ligand to label the DA uptake site in the striatum.
