EUPHORIGENIC DOSES OF COCAINE REDUCE [I-123] BETA-CIT SPECT MEASURES OF DOPAMINE TRANSPORTER AVAILABILITY IN HUMAN COCAINE ADDICTS

The in vivo potency of euphorigenic doses of intravenous cocaine for d isplacing [I-123]beta-CIT ([I-123]2 beta- carbomethoxy-3 beta-(4-iodop henyl)tropane) binding to striatal dopamine transporters (DAT) was ass essed in human cocaine addicts using single photon emission computed t omography (SPECT). Cocaine-dependent subjects (n = 6) were injected wi th [I-123]beta-CIT and imaged 24 h later under equilibrium conditions. Sequential cocaine infusions (0.28 +/- 0.03 and 0.56 +/- 0.07 mg/kg) produced significant (P < 0.0005) reductions in the specific to non-sp ecific equilibrium partition coefficient, V-3 '' (6 +/- 6 and 17 +/- 3 %), a measure proportional to DAT binding potential. Regression analys is of the legit transformed data enabled reliable determination of the Hill coefficient (0.51) and 50% displacement (ED(50)) dose of cocaine (2.8 mg/kg). These preliminary data suggest that cocaine produces beh avioral effects in humans at measurable levels of DAT occupancy.