STRIATAL [I-125] RTI-55 BINDING-SITES IN COCAINE-ABUSING HUMANS

1. Previous experiments in this laboratory found that striatal [H-3]WI N 35428 binding was increased in post mortem specimens from human coca ine users (Little et al, 1993a). Although structurally similar, prelim inary studies have suggested that [H-3]WIN 35428 and the related cocai ne congener [I-125]RTI-55 differ in some respects pharmacologically. 2 . The present experiments tested the hypothesis that striatal [I-125]R TI-55 binding would be increased, as was [H-3]WIN 35428 binding, in po st mortem specimens from cocaine users compared to matched controls. 3 . However, computer-generated parameters derived from saturation exper iments found only trends toward increased Bmax and decreased affinity (increased K-D) in the cocaine users. The magnitude of the increases w ere notably smaller than the statistically significant increases previ ously found in high affinity [H-3]WIN 35428 binding in these same subj ects. 4. Evidence from the present and earlier experiments suggests th at cocaine exposure may induce conformational changes in the dopamine transporter.