ABSTRACT
OBJECTIVE: The authors examined whether striatal dopamine transporters were altered in acutely (96 hours or less) abstinent cocaine-abusing subjects, as suggested by postmortem studies. METHOD: [123I] beta-CIT and single photon emission computed tomography were used to assess striatal dopamine transporter levels in 28 cocaine-abusing subjects and 24 comparison subjects matched as a group for age and gender. RESULTS: Results showed a significant (approximately 20%) elevation in striatal V3" values in acutely abstinent cocaine-abusing subjects relative to comparison subjects. An inverse correlation between dopamine transporter level and Hamilton Depression Rating Scale score was also observed. CONCLUSIONS: These findings indicate more modest elevations in striatal dopamine transporters in cocaine-abusing subjects than noted in previous postmortem reports and suggest a possible relationship between cocaine-related depression and dopamine transporter binding.
Subject(s)
Carrier Proteins/metabolism , Cocaine-Related Disorders/diagnosis , Corpus Striatum/diagnostic imaging , Corpus Striatum/metabolism , Dopamine/metabolism , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins , Tomography, Emission-Computed, Single-Photon , Adult , Carrier Proteins/physiology , Cocaine/analogs & derivatives , Cocaine-Related Disorders/diagnostic imaging , Cocaine-Related Disorders/metabolism , Comorbidity , Depressive Disorder/epidemiology , Depressive Disorder/metabolism , Dopamine/physiology , Dopamine Plasma Membrane Transport Proteins , Female , Humans , Iodine Radioisotopes , MaleABSTRACT
The in vivo potency of euphorigenic doses of intravenous cocaine for displacing [123I]beta-CIT ([123I]2 beta-carbomethoxy-3 beta-(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]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-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.