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

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.