Euphorigenic doses of cocaine reduce [123I]beta-CIT SPECT measures of dopamine transporter availability in human cocaine addicts.
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.
Malison
R T
RT
Clinical Neuroscience Research Unit, Connecticut Mental Health Center, New Haven, CT 06519, USA.
Best
S E
SE
Wallace
E A
EA
McCance
E
E
Laruelle
M
M
Zoghbi
S S
SS
Baldwin
R M
RM
Seibyl
J S
JS
Hoffer
P B
PB
Price
L H
LH
D002352:Carrier Proteins / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D019966:Substance-Related Disorders / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine