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.
1] Department of Bioscience, Brookhaven National Laboratory, Upton, NY, USA [2] Department of Radiology, Stony Brook University, Stony Brook, NY, USA.
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GJ
Wang
Neuroimaging Laboratory, National Institute on Alcoholism and Alcohol Abuse Intramural Program, Upton, NY, USA.
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D
Tomasi
1] Neuroimaging Laboratory, National Institute on Alcoholism and Alcohol Abuse Intramural Program, Upton, NY, USA [2] Office of Director, National Institute on Drug Abuse, Bethesda, MD, USA.
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ND
Volkow
Department of Bioscience, Brookhaven National Laboratory, Upton, NY, USA.
R
R
Wang
Neuroimaging Laboratory, National Institute on Alcoholism and Alcohol Abuse Intramural Program, Upton, NY, USA.
F
F
Telang
Department of Psychology, Stony Brook University, Stony Brook, NY, USA.
E C
EC
Caparelli
Amgen Inc, Newbury Park, CA, USA.
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E
Dunayevich
D000293:Adolescent; D000328:Adult; D001066:Appetite / Q000187:drug effects*; D016642:Bupropion / Q000008:administration & dosage*; D003463:Cues; D004032:Diet; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D054439:Ghrelin; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects*; D020738:Leptin; D008279:Magnetic Resonance Imaging; D062407:Meals / Q000523:psychology*; D009271:Naltrexone / Q000008:administration & dosage*; D009765:Obesity / Q000188:drug therapy* / Q000517:prevention & control; D019894:Peptide YY; D016896:Treatment Outcome; D015431:Weight Loss
D018765:Dopamine Uptake Inhibitors; D054439:Ghrelin; D020738:Leptin; D016642:Bupropion; D019894:Peptide YY; D009271:Naltrexone