Striatal [125I]RTI-55 binding sites in cocaine-abusing humans.

1. Previous experiments in this laboratory found that striatal [3H]WIN 35428 binding was increased in post mortem specimens from human cocaine users (Little et al, 1993a). Although structurally similar, preliminary studies have suggested that [3H]WIN 35428 and the related cocaine congener [125I]RTI-55 differ in some respects pharmacologically. 2. The present experiments tested the hypothesis that striatal [125I]RTI-55 binding would be increased, as was [3H]WIN 35428 binding, in post mortem specimens from cocaine users compared to matched controls. 3. However, computer-generated parameters derived from saturation experiments found only trends toward increased Bmax and decreased affinity (increased KD) in the cocaine users. The magnitude of the increases were notably smaller than the statistically significant increases previously found in high affinity [3H]WIN 35428 binding in these same subjects. 4. Evidence from the present and earlier experiments suggests that cocaine exposure may induce conformational changes in the dopamine transporter.