Euphorigenic doses of cocaine reduce [¹²³I]β-CIT SPECT measures of dopamine transporter availability in human cocaine addicts

The in vivo potency of euphorigenic doses of intravenous cocaine for displacing [¹²³I]β-CIT ([¹²³I]2 β-carbomethoxy-3 β-(4-iodophenyl)tropane) binding to striatal dopamine transporters (DAT) was assessed in human cocaine addicts using single photon emission computed tomography (SPECT). Cocaine-dependent subjects (n=6) were injected with [¹²³I]β-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-specific equilibrium partition coefficient, V₃″ (6±6 and 17±3%), a measure proportional to DAT binding potential. Regression analysis of the logit transformed data enabled reliable determination of the Hill coefficient (0.51) and 50% displacement (ED₅₀) dose of cocaine (2.8 mg/kg). These preliminary data suggest that cocaine produces behavioral effects in humans at measurable levels of DAT occupancy.