Imaging dopamine transmission in cocaine dependence: link between neurochemistry and response to treatment - PubMed (original) (raw)

Diana Martinez et al. Am J Psychiatry. 2011 Jun.

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Abstract

Objective: Previous research has shown that dopamine signaling in the limbic striatum is crucial for selecting adaptive, motivated behavior and that disrupted dopamine transmission is associated with impulsive and maladaptive behavior. In humans, positron emission tomography (PET) imaging studies have shown that cocaine dependence is associated with the dysregulation of striatal dopamine signaling, which is linked to cocaine-seeking behavior. The goal of the present study was to investigate whether this association applies to the treatment setting. The authors hypothesized that dopamine signaling in the limbic striatum would be associated with response to a behavioral treatment that uses positive reinforcement to replace impulsive cocaine use with constructive personal goals.

Method: Prior to treatment, cocaine-dependent subjects underwent two PET scans using [(11)C]raclopride, before and after the administration of a stimulant (methylphenidate), for measurement of striatal dopamine D(2/3) receptor binding and presynaptic dopamine release.

Results: Both of the outcome measures were lower in the volunteers who did not respond to treatment than in those who experienced a positive treatment response.

Conclusions: These findings provide insight into the neurochemistry of treatment response and show that low dopamine transmission is associated with treatment failure. In addition, these data suggest that the combination of behavioral treatment with methods that increase striatal dopamine signaling might serve as a therapeutic strategy for cocaine dependence.

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Conflict of interest statement

Disclosure/Conflicts of Interest:

The authors report no conflicts of interest associated with the content of this manuscript.

Diana Martinez: no disclosures

Kenneth Carpentar: no disclosures

Fei Liu: no disclosures

Mark Slifstein: is a consultant for Glaxo-Smith-Kline and Amgen.

Allegra Broft: no disclosures

Alessandra Calvo-Friedman: no disclosures

Dileep Kumar: no disclosures

Ronald Van Heertum: no disclosures

Herbert D Kleber: is a consultant for Abbott Labs, The Grunenthal Group, Johnson & Johnson, Purdue Pharma, Reckett Benckiser, Alkermes Pharmaceuticals

Edward Nunes: no disclosures

Figures

Figure 1

Figure 1

A) Plot of all cocaine dependent subjects (n = 25) showing the amount of voucher money earned for cocaine-negative urine samples (range 0–0 – 0–977.50). The subjects’ response to treatment shows a bimodal distribution, which was used to classify subjects as responders or non-responders. B) Comparison of the average number of cocaine-negative urines provided over 12 weeks in the non-responders and responders (range 0–36). The values are the average and standard deviation for each group.

Figure 2

Figure 2

A) Average [11C]raclopride D2/3 receptor binding (BPND) in the treatment responders (top) and non-responders (bottom). The scans shown are before (left) and after (right) 60 mg PO methylphenidate administration, which increases extracellular dopamine so that fewer D2/3 receptors are available to bind to [11C]raclopride. The color bar shows the values for BPND. B) Bar graphs showing the differences between the treatment responders and non-responders in the limbic striatum for (left) BPND (pre-methylphenidate D2/3 receptor binding) and (right) ΔBPND, the percent decrease in methylphenidate-induced [11C]raclopride binding. These data show that treatment responders had higher dopamine D2/3 receptor binding and greater pre-synaptic dopamine release compared to non-responders in the limbic striatum.

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