OBJECTIVE: Animal data suggest that the strong euphoriant effects of
cocaine are related to the drug's enhancement of available dopamine at the
synaptic cleft. The authors' goal was to determine whether this mechanism
is the same in humans because the development of putative pharmacological
agents for treatment of cocaine dependence depends on this knowledge.
METHOD: Positron emission tomography with [11C]raclopride was used to
examine the effects of the intravenous administration of 48 mg of cocaine
(a typical "street" dose) on the occupancy of dopamine 2 receptors in the
putamen of 11 self-identified intravenous drug abusers. RESULTS: All 11
subjects reported subjective stimulation and euphoria in response to
cocaine administration. Radioligand occupancy at dopamine receptors was
decreased significantly after cocaine administration, suggesting that
higher dopamine concentrations were competing at the receptor site.
CONCLUSIONS: These results support the concept of dopamine system
involvement in human cocaine abuse.