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 [11C]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 [11C]raclopride binding values in the ventral limbic striatum and putamen. Individual differences in the magnitude of the [11C]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.