Regional distribution of the serotonin transport complex in human brain, identified with 3H-paroxetine, 3H-citalopram and 3H-imipramine.

1. Regional distribution of the serotonin transport complex was studied in 12 different brain areas from human brains. The serotonin uptake complex was measured with 3H-paroxetine, and 3H-imipramine. The binding site density was highest in the nucleus of raphé, medium in the basal ganglia, and lowest in cortical areas. The specific binding measured with 3H-paroxetine and 3H-citalopram was compared with the high affinity 3H-imipramine binding determined with either 100 microM 5HT or 1 microM imipramine as non specific displacers. 3H-paroxetine and 3H-citalopram allowed a more precise determination of Bmax, and are both good ligands for the serotonin uptake site, but the determinations with 3H-imipramine were within the same range. 2. Protease digestion of brain membranes showed that the binding site measured with all three ligands disappeared with the same rate as other membrane proteins, and not faster as might be expected from the literature. 3. Left/right hemisphere distribution was measured in cortical tissue from 6 brains using 3H-paroxetine. No difference between the two hemispheres was found. In one brain from a lithium treated patient a very low binding was measured, possibly indicating that the lithium treatment had decreased the serotonin uptake mechanism.