High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims

Cocaine mediates its powerful reinforcement by binding to recognition sites on the dopamine (DA) transporter. The phar-macological identity of cocaine recognition sites and their rel-evance to dopamine transport function has remained unclear. Ligand binding studies with transport inhibitors and cocaine congeners have provided evidence for multiple sites or “states ” of the DA transporter. The potent cocaine congener rHIWIN 35,428 {(CFT), 2B-carbomethoxy-3-(4-fluorophenyl)-tropane} has been shown to recognize high and low affinity binding sites on the DA transporter. We have used rH]WIN 35,428 to map and quantify the high affinity cocaine recognition site on the DA transporter in victims of fatal cocaine overdose. Region-of-interest densitometnc analysis of the autoradio-grams demonstrated a 2- to 3-fold elevation in the apparen