Effect of combined naltrexone and bupropion therapy on the brain's reactivity to food cues

G-J Wang, D Tomasi, N D Volkow, R Wang, F Telang, E C Caparelli, E Dunayevich, G-J Wang, D Tomasi, N D Volkow, R Wang, F Telang, E C Caparelli, E Dunayevich

Abstract

Objective: The significant weight loss observed with combination naltrexone-sustained release (SR) 32 mg and bupropion SR 360 mg (NB32) therapy is thought to be due, in part, to bupropion stimulation of hypothalamic pro-opiomelanocortin (POMC) neurons, and naltrexone blockade of opioid receptor-mediated POMC autoinhibition, but the neurobiological mechanisms are not fully understood. We assessed changes in brain reactivity to food cues before and after NB32 treatment.

Methods: Forty women (31.1±8.1 years; body mass index: 32.5±3.9) received 4 weeks of NB32 or placebo, and were instructed to maintain their dietary and exercise habits. Functional magnetic resonance imaging responses (analyzed using SPM2 and clusters (>100 pixels)) to a 5-min food video (preparation of the subject's favorite food) and a 5-min neutral video (manipulation of neutral objects) under conditions of mild food deprivation (∼14 h) were assessed before and after treatment.

Results: The food cues video induced positive brain activation in visual and prefrontal cortices, insula and subcortical brain regions. The group-by-treatment interaction on regional brain activation was significant and showed that whereas NB32 attenuated the activation in the hypothalamus in response to food cues (P<0.01), it enhanced activation in regions involved in inhibitory control (anterior cingulate), internal awareness (superior frontal, insula, superior parietal) and memory (hippocampal) regions (whole-brain analysis; P<0.05).

Conclusions: Blunting the hypothalamic reactivity to food cues while enhancing the activation of regions involved with self-control and internal awareness by NB32 might underlie its therapeutic benefits in obesity.

Figures

Figure 1
Figure 1
fMRI paradigm. (a) Example of the timeline of the food-video stimulation. Each 600 seconds video contained 150 seconds control video (CV) fragments at its beginning and end, as well as 5-60 second food video (FV) fragments showing serving and consumption of the subject's favorite food items. (b) The general lineal model implemented in SPM2 was based on a castle design with 5 regressors modeling the FV epochs, which contrasted the FV fragments against the CV fragments.
Figure 2
Figure 2
The effect of NB32 and placebo on brain activity during food cue stimulation. Significant activated clusters during FV stimulation. SPG, superior parietal gyrus; ACG, anterior cingulate gyrus; PCG, posterior cingulate gyrus; IFG, inferior frontal gyrus; THL, thalamus; INS, insula; MB, midbrain; OCC, occipital cortex; HIP, hippocampus; CBL, cerebellum.
Figure 3
Figure 3
The greater effect of NB32 as compared with placebo in response to visual food cues.

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