In vivo binding of [125I] RTI‐55 to dopamine transporters: Pharmacology and regional distribution with autoradiography

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Abstract
Previous studies have demonstrated that para‐substituted WIN 35,065‐2 analogs of cocaine show high binding affinity for dopamine uptake sites both in vitro and in vivo, and inhibit DA uptake in vitro. These analogs also produce potent cocaine‐like behavioral effects in various procedures. The purpose of the present studies was to evaluate the iodinated WIN 35,065‐2 analog [125I] RTI‐55 as an in vivo ligand for the DA transporter. Following intravenous injection in mice, [125I] RTI‐55 showed highest accumulation in areas with high densities of dopamine uptake sites. Light microscopic autoradiography was used to examine binding with higher resolution. Displacement studies demonstrated that [125I] RTI‐55 binding in dopamine containing regions, striatum and olfactory tubercles, was saturable and inhibited by other cocaine analogs. GBR 12909 and WIN 35,428 significantly inhibited [125I] RTI‐55 binding in striatum, while paroxetine significantly inhibited hypothalamic binding but had little effect in striatum. The latter finding suggests that [125I] RTI‐55 also binds to the serotonin transporter. Haloperidol had no effect on [125I] RTI‐55 binding in any brain region measured. In addition, treatment of animals with the dopamine neurotoxin MPTP caused significant reductions in striatal [125I] RTI‐55 binding. The results of these studies indicate that [125I] RTI‐55 binds primarily to the dopamine transporter in the mouse striatum in vivo. Published 1992 Wiley‐Liss, Inc.