Impact of DCS-facilitated cue exposure therapy on brain activation to cocaine cues in cocaine dependence

Abstract

Background: The development of addiction is marked by a pathological associative learning process that imbues incentive salience to stimuli associated with drug use. Recent efforts to treat addiction have targeted this learning process using cue exposure therapy augmented with d-cycloserine (DCS), a glutamatergic agent hypothesized to enhance extinction learning. To better understand the impact of DCS-facilitated extinction on neural reactivity to drug cues, the present study reports fMRI findings from a randomized, double-blind, placebo-controlled trial of DCS-facilitated cue exposure for cocaine dependence.

Methods: Twenty-five participants completed two MRI sessions (before and after intervention), with a cocaine-cue reactivity fMRI task. The intervention consisted of 50mg of DCS or placebo, combined with two sessions of cocaine cue exposure and skills training.

Results: Participants demonstrated cocaine cue activation in a variety of brain regions at baseline. From the pre- to post-study scan, participants experienced decreased activation to cues in a number of regions (e.g., accumbens, caudate, frontal poles). Unexpectedly, placebo participants experienced decreases in activation to cues in the left angular and middle temporal gyri and the lateral occipital cortex, while DCS participants did not.

Conclusions: Three trials of DCS-facilitated cue exposure therapy for cocaine dependence have found that DCS either increases or does not significantly impact response to cocaine cues. The present study adds to this literature by demonstrating that DCS may prevent extinction to cocaine cues in temporal and occipital brain regions. Although consistent with past research, results from the present study should be considered preliminary until replicated in larger samples.

Trial registration: ClinicalTrials.gov NCT00759473.

Keywords: Cocaine dependence; Cue reactivity; DCS; Exposure therapy; d-Cycloserine; fMRI.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1

Baseline Analyses. Top Panel: SPM map of blood oxygen level dependent (BOLD) response to cocaine cues minus neutral objects across all participants using a voxelwise threshold of z > 3.50 and a cluster threshold of p < 0.05. Bottom Panel: SPM map of the association between subjective craving and BOLD response to cocaine minus neutral cues using a voxelwise threshold of z > 3.53 and a cluster threshold of p < 0.05. Crosshair is centered on the peak-activated voxel of a cluster in the anterior division of the supramarginal gyrus of the parietal lobe.

Figure 2

2×2 mixed-effects ANOVA results. Top Panel: SPM map of blood oxygen level dependent (BOLD) response to cocaine cues minus neutral objects at pre-scan versus post-scan using a voxelwise threshold of z > 3.32 and a cluster threshold of p < 0.05. Bottom Panel: SPM map of the interaction between medication group (D-cycloserine vs. placebo) and MRI session (pre-scan vs. post-scan) on blood oxygen level dependent (BOLD) response to cocaine cues minus neutral objects using a voxelwise threshold of z > 2.43 and a cluster threshold of p < 0.05. Crosshair is centered on the peak-activated voxel of a cluster including the left angular gyrus, lateral occipital cortex, and middle temporal gyrus.