Elsevier

Biological Psychiatry

Volume 65, Issue 10, 15 May 2009, Pages 846-850
Biological Psychiatry

Archival Report
Striatal Dopamine Responses to Intranasal Cocaine Self-Administration in Humans

https://doi.org/10.1016/j.biopsych.2009.01.021Get rights and content

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.

Section snippets

Subjects

Ten nondependent cocaine users (aged 23.7 ± 2.8; two women, eight men; see Table 1) were recruited from the community through advertisements in local newspapers. For all subjects, the primary and preferred route of self-administration was intranasal. All were free of current or past substance dependence, as determined by a semistructured clinical interview for DSM-IV diagnoses (10). Six of the 10 participants were current light smokers with a score of less than 3 on the Fagerstrom Test for

Plasma Cocaine

Plasma concentrations of cocaine differed significantly between the test sessions as reflected by a Test × Time interaction [F(3,21) = 35.3, p ≤ .0001]. Plasma cocaine levels peaked at 45 min post–cocaine self-administration, midscan (mean ± SD: 149 ± 44 ng/mL). Cocaine was not detected in plasma on the drug-free (placebo) test day or on the baseline measure before cocaine self-administration.

PET Aata: Analyses of t Maps

A voxelwise analysis revealed a significant decrease in [11C]raclopride BP values on the test with

Discussion

We investigated the effect of intranasal cocaine self-administration on striatal DA responses in nondependent cocaine users. There were two primary novel findings. First, cocaine self-administration, compared with placebo powder, decreased [11C]raclopride binding levels and did so preferentially within the ventral limbic striatum and postcommissural putamen. Second, individual differences in the magnitude of the cocaine-induced [11C]raclopride response in the ventral striatum were predicted by

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