Striatal Dopamine Responses to Intranasal Cocaine Self-Administration in Humans

Background: The effect of self-administered cocaine on extracellular dopamine (DA) levels has not been measured in humans. Methods: Ten nondependent cocaine users underwent positron emission tomography [C-11]raclopride scans following intranasal self-administration of cocaine hydrochloride (1.0 mg/kg) and placebo powder. Results: Compared with placebo, intranasal cocaine self-administration decreased [C-11]raclopride binding values in the ventral limbic striatum and putamen. Individual differences in the magnitude of the [C-11]raclopride response in the ventral striatum were predicted by lifetime histories of stimulant drug use. Conclusions: The results suggest that 1) intranasal cocaine self-administration increases synaptic DA levels in human striatum and 2) prior use of stimulant drugs on the street is associated with progressively greater cocaine-induced DA responses. These dopaminergic effects might influence susceptibility to drug-seeking behavior and the progression to substance abuse.