Key Points
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The rise in the prevalence of obesity has prompted numerous research efforts dedicated to better understanding the mechanisms underlying this trend
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A major focus of such research is the contribution of overeating, which can produce a positive energy balance and result in body weight gain
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More recently, select endocrine factors associated with food intake and body weight have been shown to interact with neural systems of reward
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Preclinical and clinical studies suggest that food reward and alterations in reward pathways may progress to food addiction
Abstract
With rising rates of obesity, research continues to explore the contributions of homeostatic and hedonic mechanisms related to eating behaviour. In this Review, we synthesize the existing information on select biological mechanisms associated with reward-related food intake, dealing primarily with consumption of highly palatable foods. In addition to their established functions in normal feeding, three primary peripheral hormones (leptin, ghrelin and insulin) play important parts in food reward. Studies in laboratory animals and humans also show relationships between hyperphagia or obesity and neural pathways involved in reward. These findings have prompted questions regarding the possibility of addictive-like aspects in food consumption. Further exploration of this topic may help to explain aberrant eating patterns, such as binge eating, and provide insight into the current rates of overweight and obesity.
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References
Kobeissy, F. H., Jeung, J. A., Warren, M. W., Geier, J. E. & Gold, M. S. Changes in leptin, ghrelin, growth hormone and neuropeptide-Y after an acute model of MDMA and methamphetamine exposure in rats. Addict. Biol. 13, 15–25 (2008).
Gold, M. S. From bedside to bench and back again: a 30-year saga. Physiol. Behav. 104, 157–161 (2011).
Avena, N. M., Rada, P. & Hoebel, B. G. Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci. Biobehav. Rev. 32, 20–39 (2008).
Johnson, P. M. & Kenny, P. J. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat. Neurosci. 13, 635–641 (2010).
Oswald, K. D., Murdaugh, D. L., King, V. L. & Boggiano, M. M. Motivation for palatable food despite consequences in an animal model of binge eating. Int. J. Eat. Disord. 44, 203–211 (2011).
Gearhardt, A. N. et al. An examination of the food addiction construct in obese patients with binge eating disorder. Int. J. Eat. Disord. 45, 657–663 (2012).
Davis, C. et al. Evidence that 'food addiction' is a valid phenotype of obesity. Appetite 57, 711–717 (2011).
Edge, P. J. & Gold, M. S. Drug withdrawal and hyperphagia: lessons from tobacco and other drugs. Curr. Pharm. Des. 17, 1173–1179 (2011).
Keen-Rhinehart, E., Ondek, K. & Schneider, J. E. Neuroendocrine regulation of appetitive ingestive behavior. Front. Neurosci. 7, 213 (2013).
Suzuki, K., Simpson, K. A., Minnion, J. S., Shillito, J. C. & Bloom, S. R. The role of gut hormones and the hypothalamus in appetite regulation. Endocr. J. 57, 359–372 (2010).
Sam, A. H., Troke, R. C., Tan, T. M. & Bewick, G. A. The role of the gut/brain axis in modulating food intake. Neuropharmacology 63, 46–56 (2012).
Rui, L. Brain regulation of energy balance and body weight. Rev. Endocr. Metab. Disord. 14, 387–407 (2013).
Scott, R., Tan, T. & Bloom, S. Gut hormones and obesity: physiology and therapies. Vitam. Horm. 91, 143–194 (2013).
Fulton, S. et al. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51, 811–822 (2006).
Hommel, J. D. et al. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51, 801–810 (2006).
Bouret, S. G., Draper, S. J. & Simerly, R. B. Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304, 108–110 (2004).
Bruijnzeel, A. W., Corrie, L. W., Rogers, J. A. & Yamada, H. Effects of insulin and leptin in the ventral tegmental area and arcuate hypothalamic nucleus on food intake and brain reward function in female rats. Behav. Brain Res. 219, 254–264 (2011).
Morton, G. J., Blevins, J. E., Kim, F., Matsen, M. & Figlewicz, D. P. The action of leptin in the ventral tegmental area to decrease food intake is dependent on Jak-2 signaling. Am. J. Physiol. Endocrinol. Metab. 297, E202–E210 (2009).
Leinninger, G. M. et al. Leptin acts via leptin receptor-expressing lateral hypothalamic neurons to modulate the mesolimbic dopamine system and suppress feeding. Cell Metab. 10, 89–98 (2009).
Kumer, S. C. & Vrana, K. E. Intricate regulation of tyrosine hydroxylase activity and gene expression. J. Neurochem. 67, 443–462 (1996).
Leinninger, G. M. et al. Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell Metab. 14, 313–323 (2011).
Opland, D. et al. Loss of neurotensin receptor-1 disrupts the control of the mesolimbic dopamine system by leptin and promotes hedonic feeding and obesity. Mol. Metab. 2, 423–434 (2013).
Leshan, R. L. et al. Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine- and amphetamine-regulated transcript neurons of the extended central amygdala. J. Neurosci. 30, 5713–5723 (2010).
Thompson, J. L. & Borgland, S. L. Presynaptic leptin action suppresses excitatory synaptic transmission onto ventral tegmental area dopamine neurons. Biol. Psychiatry 73, 860–868 (2013).
Bruijnzeel, A. W., Qi, X. & Corrie, L. W. Anorexic effects of intra-VTA leptin are similar in low-fat and high-fat-fed rats but attenuated in a subgroup of high-fat-fed obese rats. Pharmacol. Biochem. Behav. 103, 573–581 (2013).
Scarpace, P. J. et al. Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged leptin action in either region cross-desensitizes. Neuropharmacology 65, 90–100 (2013).
Matheny, M., Shapiro, A., Tumer, N. & Scarpace, P. J. Region-specific diet-induced and leptin-induced cellular leptin resistance includes the ventral tegmental area in rats. Neuropharmacology 60, 480–487 (2011).
Rothemund, Y. et al. Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals. Neuroimage 37, 410–421 (2007).
Grosshans, M. et al. Association of leptin with food cue-induced activation in human reward pathways. Arch. Gen. Psychiatry 69, 529–537 (2012).
Rosenbaum, M., Sy, M., Pavlovich, K., Leibel, R. L. & Hirsch, J. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J. Clin. Invest. 118, 2583–2591 (2008).
Hinkle, W., Cordell, M., Leibel, R., Rosenbaum, M. & Hirsch, J. Effects of reduced weight maintenance and leptin repletion on functional connectivity of the hypothalamus in obese humans. PLoS ONE 8, e59114 (2013).
Geliebter, A., Hashim, S. A. & Gluck, M. E. Appetite-related gut peptides, ghrelin, PYY, and GLP-1 in obese women with and without binge eating disorder (BED). Physiol. Behav. 94, 696–699 (2008).
Geliebter, A., Yahav, E. K., Gluck, M. E. & Hashim, S. A. Gastric capacity, test meal intake, and appetitive hormones in binge eating disorder. Physiol. Behav. 81, 735–740 (2004).
Geliebter, A., Gluck, M. E. & Hashim, S. A. Plasma ghrelin concentrations are lower in binge-eating disorder. J. Nutr. 135, 1326–1330 (2005).
Monteleone, P. et al. Circulating ghrelin is decreased in non-obese and obese women with binge eating disorder as well as in obese non-binge eating women, but not in patients with bulimia nervosa. Psychoneuroendocrinology 30, 243–250 (2005).
Abizaid, A. et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J. Clin. Invest. 116, 3229–3239 (2006).
Lindqvist, A., de la Cour, C. D., Stegmark, A., Hakanson, R. & Erlanson-Albertsson, C. Overeating of palatable food is associated with blunted leptin and ghrelin responses. Regul. Pept. 130, 123–132 (2005).
Perello, M. et al. Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol. Psychiatry 67, 880–886 (2010).
Skibicka, K. P., Hansson, C., Alvarez-Crespo, M., Friberg, P. A. & Dickson, S. L. Ghrelin directly targets the ventral tegmental area to increase food motivation. Neuroscience 180, 129–137 (2011).
Egecioglu, E. et al. Ghrelin increases intake of rewarding food in rodents. Addict. Biol. 15, 304–311 (2010).
Jerlhag, E., Janson, A. C., Waters, S. & Engel, J. A. Concomitant release of ventral tegmental acetylcholine and accumbal dopamine by ghrelin in rats. PLoS ONE 7, e49557 (2012).
Skibicka, K. P. et al. Divergent circuitry underlying food reward and intake effects of ghrelin: dopaminergic VTA-accumbens projection mediates ghrelin's effect on food reward but not food intake. Neuropharmacology 73, 274–283 (2013).
Skibicka, K. P., Hansson, C., Egecioglu, E. & Dickson, S. L. Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression. Addict. Biol. 17, 95–107 (2012).
Skibicka, K. P., Shirazi, R. H., Hansson, C. & Dickson, S. L. Ghrelin interacts with neuropeptide Y Y1 and opioid receptors to increase food reward. Endocrinology 153, 1194–1205 (2012).
Kawahara, Y. et al. Food reward-sensitive interaction of ghrelin and opioid receptor pathways in mesolimbic dopamine system. Neuropharmacology 67, 395–402 (2013).
Monteleone, P. et al. Gastroenteric hormone responses to hedonic eating in healthy humans. Psychoneuroendocrinology 38, 1435–1441 (2013).
Monteleone, P. et al. Hedonic eating is associated with increased peripheral levels of ghrelin and the endocannabinoid 2-arachidonoyl-glycerol in healthy humans: a pilot study. J. Clin. Endocrinol. Metab. 97, E917–E924 (2012).
Banks, W. A., Owen, J. B. & Erickson, M. A. Insulin in the brain: there and back again. Pharmacol. Ther. 136, 82–93 (2012).
Figlewicz, D. P., Evans, S. B., Murphy, J., Hoen, M. & Baskin, D. G. Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat. Brain Res. 964, 107–115 (2003).
Labouèbe, G. et al. Insulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids. Nat. Neurosci. 16, 300–308 (2013).
Figlewicz, D. P., Bennett, J. L., Aliakbari, S., Zavosh, A. & Sipols, A. J. Insulin acts at different CNS sites to decrease acute sucrose intake and sucrose self-administration in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 295, R388–R394 (2008).
Mebel, D. M., Wong, J. C., Dong, Y. J. & Borgland, S. L. Insulin in the ventral tegmental area reduces hedonic feeding and suppresses dopamine concentration via increased reuptake. Eur. J. Neurosci. 36, 2336–2346 (2012).
Könner, A. C. et al. Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis. Cell Metab. 13, 720–728 (2011).
Jauch-Chara, K. et al. Intranasal insulin suppresses food intake via enhancement of brain energy levels in humans. Diabetes 61, 2261–2268 (2012).
Hallschmid, M., Higgs, S., Thienel, M., Ott, V. & Lehnert, H. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women. Diabetes 61, 782–789 (2012).
Kroemer, N. B. et al. (Still) longing for food: insulin reactivity modulates response to food pictures. Hum. Brain Mapp. 34, 2367–2380 (2013).
Stice, E., Figlewicz, D. P., Gosnell, B. A., Levine, A. S. & Pratt, W. E. The contribution of brain reward circuits to the obesity epidemic. Neurosci. Biobehav. Rev. 37, 2047–2058 (2013).
Kenny, P. J. Reward mechanisms in obesity: new insights and future directions. Neuron 69, 664–679 (2011).
Volkow, N. D. & Wise, R. A. How can drug addiction help us understand obesity? Nat. Neurosci. 8, 555–560 (2005).
[No authors listed] The neural basis of feeding and reward. Festschrift dedicated to Dr Bart Hoebel. January 14, 2011. Princeton, New Jersey, USA. Physiol. Behav. 104, 1–177 (2011).
Blumenthal, D. M. & Gold, M. S. Neurobiology of food addiction. Curr. Opin. Clin. Nutr. Metab. Care 13, 359–365 (2010).
DiLeone, R. J., Taylor, J. R. & Picciotto, M. R. The drive to eat: comparisons and distinctions between mechanisms of food reward and drug addiction. Nat. Neurosci. 15, 1330–1335 (2012).
Pedram, P. et al. Food addiction: its prevalence and significant association with obesity in the general population. PLoS ONE 8, e74832 (2013).
Volkow, N. D., Wang, G. J., Tomasi, D. & Baler, R. D. Obesity and addiction: neurobiological overlaps. Obes. Rev. 14, 2–18 (2013).
Ochner, C. N., Barrios, D. M., Lee, C. D. & Pi-Sunyer, F. X. Biological mechanisms that promote weight regain following weight loss in obese humans. Physiol. Behav. 120, 106–113 (2013).
Ikemoto, S. & Panksepp, J. The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res. Brain Res. Rev. 31, 6–41 (1999).
Hajnal, A. & Norgren, R. Accumbens dopamine mechanisms in sucrose intake. Brain Res. 904, 76–84 (2001).
Bassareo, V. & Di Chiara, G. Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments. Neuroscience 89, 637–641 (1999).
Hernández, L., Paredes, D. & Rada, P. Feeding behavior as seen through the prism of brain microdialysis. Physiol. Behav. 104, 47–56 (2011).
Beeler, J. A., Frazier, C. R. & Zhuang, X. Putting desire on a budget: dopamine and energy expenditure, reconciling reward and resources. Front. Integr. Neurosci. 6, 49 (2012).
Geiger, B. M. et al. Evidence for defective mesolimbic dopamine exocytosis in obesity-prone rats. FASEB J. 22, 2740–2746 (2008).
Geiger, B. M. et al. Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity. Neuroscience 159, 1193–1199 (2009).
Rada, P., Bocarsly, M. E., Barson, J. R., Hoebel, B. G. & Leibowitz, S. F. Reduced accumbens dopamine in Sprague–Dawley rats prone to overeating a fat-rich diet. Physiol. Behav. 101, 394–400 (2010).
Hansen, H. H., Jensen, M. M., Overgaard, A., Weikop, P. & Mikkelsen, J. D. Tesofensine induces appetite suppression and weight loss with reversal of low forebrain dopamine levels in the diet-induced obese rat. Pharmacol. Biochem. Behav. 110, 265–271 (2013).
Alsiö, J. et al. Dopamine D1 receptor gene expression decreases in the nucleus accumbens upon long-term exposure to palatable food and differs depending on diet-induced obesity phenotype in rats. Neuroscience 171, 779–787 (2010).
Alsiö, J. et al. Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats. Neurosci. Lett. 559, 18–23 (2014).
van de Giessen, E., la Fleur, S. E., de Bruin, K., van den Brink, W. & Booij, J. Free-choice and no-choice high-fat diets affect striatal dopamine D2/3 receptor availability, caloric intake, and adiposity. Obesity (Silver Spring) 20, 1738–1740 (2012).
van de Giessen, E. et al. High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity. Int. J. Obes. (Lond.) 37, 754–757 (2013).
Speed, N. et al. Impaired striatal Akt signaling disrupts dopamine homeostasis and increases feeding. PLoS ONE 6, e25169 (2011).
Fetissov, S. O., Meguid, M. M., Sato, T. & Zhang, L. H. Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake. Am. J. Physiol. Regul. Integr. Comp. Physiol. 283, R905–R910 (2002).
Trifilieff, P. & Martinez, D. Imaging addiction: D2 receptors and dopamine signaling in the striatum as biomarkers for impulsivity. Neuropharmacology 76, 498–509 (2014).
Marco, A., Schroeder, M. & Weller, A. Feeding and reward: ontogenetic changes in an animal model of obesity. Neuropharmacology 62, 2447–2454 (2012).
Kim, K. S. et al. Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors. J. Biol. Chem. 285, 8905–8917 (2010).
Corwin, R. L. & Wojnicki, F. H. Baclofen, raclopride, and naltrexone differentially affect intake of fat and sucrose under limited access conditions. Behav. Pharmacol. 20, 537–548 (2009).
Pritchett, C. E. & Hajnal, A. Obesogenic diets may differentially alter dopamine control of sucrose and fructose intake in rats. Physiol. Behav. 104, 111–116 (2011).
Wong, K. J., Wojnicki, F. H. & Corwin, R. L. Baclofen, raclopride, and naltrexone differentially affect intake of fat/sucrose mixtures under limited access conditions. Pharmacol. Biochem. Behav. 92, 528–536 (2009).
Koerber, J., Goodman, D., Barnes, J. L. & Grimm, J. W. The dopamine D2 antagonist eticlopride accelerates extinction and delays reacquisition of food self-administration in rats. Behav. Pharmacol. 24, 633–639 (2013).
van de Giessen, E., de Bruin, K., la Fleur, S. E., van den Brink, W. & Booij, J. Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats. Eur. Neuropsychopharmacol. 22, 290–299 (2012).
Avena, N. M., Bocarsly, M. E., Rada, P., Kim, A. & Hoebel, B. G. After daily bingeing on a sucrose solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalance. Physiol. Behav. 94, 309–315 (2008).
Avena, N. M., Rada, P. & Hoebel, B. G. Underweight rats have enhanced dopamine release and blunted acetylcholine response in the nucleus accumbens while bingeing on sucrose. Neuroscience 156, 865–871 (2008).
Baik, J. H. Dopamine signaling in reward-related behaviors. Front. Neural Circuits 7, 152 (2013).
Pickering, C., Alsiö, J., Hulting, A. L. & Schiöth, H. B. Withdrawal from free-choice high-fat high-sugar diet induces craving only in obesity-prone animals. Psychopharmacology (Berl.) 204, 431–443 (2009).
de Jong, J. W., Meijboom, K. E., Vanderschuren, L. J. & Adan, R. A. Low control over palatable food intake in rats is associated with habitual behavior and relapse vulnerability: individual differences. PLoS ONE 8, e74645 (2013).
Colantuoni, C. et al. Excessive sugar intake alters binding to dopamine and μ-opioid receptors in the brain. Neuroreport 12, 3549–3452 (2001).
Bello, N. T., Lucas, L. R. & Hajnal, A. Repeated sucrose access influences dopamine D2 receptor density in the striatum. Neuroreport 13, 1575–1578 (2002).
Hajnal, A. & Norgren, R. Repeated access to sucrose augments dopamine turnover in the nucleus accumbens. Neuroreport 13, 2213–2216 (2002).
Bello, N. T., Sweigart, K. L., Lakoski, J. M., Norgren, R. & Hajnal, A. Restricted feeding with scheduled sucrose access results in an upregulation of the rat dopamine transporter. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284, R1260–R1268 (2003).
Chandler-Laney, P. C. et al. A history of caloric restriction induces neurochemical and behavioral changes in rats consistent with models of depression. Pharmacol. Biochem. Behav. 87, 104–114 (2007).
Davis, J. F. et al. Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat. Behav. Neurosci. 122, 1257–1263 (2008).
Rada, P., Avena, N. M. & Hoebel, B. G. Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience 134, 737–744 (2005).
Avena, N. M., Rada, P., Moise, N. & Hoebel, B. G. Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly and eliminates the acetylcholine satiety response. Neuroscience 139, 813–820 (2006).
Liang, N. C., Hajnal, A. & Norgren, R. Sham feeding corn oil increases accumbens dopamine in the rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R1236–R1239 (2006).
Avena, N. & Hoebel, B. in Food and Addiction: A Comprehensive Handbook Ch. 31 (eds Brownell, K. & Gold, M.) 206–213 (Oxford University Press, 2012).
Colantuoni, C. et al. Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence. Obes. Res. 10, 478–488 (2002).
Avena, N. M., Long, K. A. & Hoebel, B. G. Sugar-dependent rats show enhanced responding for sugar after abstinence: evidence of a sugar deprivation effect. Physiol. Behav. 84, 359–362 (2005).
Wilson, G. T. Eating disorders, obesity and addiction. Eur. Eat. Disord. Rev. 18, 341–351 (2010).
Ziauddeen, H., Farooqi, I. S. & Fletcher, P. C. Obesity and the brain: how convincing is the addiction model? Nat. Rev. Neurosci. 13, 279–286 (2012).
Wang, G. J. et al. Brain dopamine and obesity. Lancet 357, 354–357 (2001).
Haltia, L. T. et al. Effects of intravenous glucose on dopaminergic function in the human brain in vivo. Synapse 61, 748–756 (2007).
Volkow, N. D. et al. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. Neuroimage 42, 1537–1543 (2008).
Dunn, J. P. et al. Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity. Diabetes Care 35, 1105–1111 (2012).
Volkow, N. D. et al. Brain dopamine is associated with eating behaviors in humans. Int. J. Eat. Disord. 33, 136–142 (2003).
Wang, G. J. et al. Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity (Silver Spring) 19, 1601–1608 (2011).
Broft, A. et al. Striatal dopamine in bulimia nervosa: a PET imaging study. Int. J. Eat. Disord. 45, 648–656 (2012).
Wilcox, C. E., Braskie, M. N., Kluth, J. T. & Jagust, W. J. Overeating behavior and striatal dopamine with 6-[F]-fluoro-l-m-tyrosine PET. J. Obes. http://dx.doi.org/10.1155/2010/909348 (2010).
Lee, B. et al. Striatal dopamine D2/D3 receptor availability is reduced in methamphetamine dependence and is linked to impulsivity. J. Neurosci. 29, 14734–14740 (2009).
Buckholtz, J. W. et al. Dopaminergic network differences in human impulsivity. Science 329, 532 (2010).
Eisenberg, D. T. et al. Examining impulsivity as an endophenotype using a behavioral approach: a DRD2 TaqI A and DRD4 48-bp VNTR association study. Behav. Brain Funct. 3, 2 (2007).
Noble, E. P. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am. J. Med. Genet. B Neuropsychiatr. Genet. 116B, 103–125 (2003).
Hardman, C. A., Rogers, P. J., Timpson, N. J. & Munafo, M. R. Lack of association between DRD2 and OPRM1 genotypes and adiposity. Int. J. Obes. (Lond.) 38, 730–736 (2014).
Epstein, L. H. et al. Food reinforcement, the dopamine D2 receptor genotype, and energy intake in obese and nonobese humans. Behav. Neurosci. 121, 877–886 (2007).
Winkler, J. K. et al. TaqIA polymorphism in dopamine D2 receptor gene complicates weight maintenance in younger obese patients. Nutrition 28, 996–1001 (2012).
Stice, E., Spoor, S., Bohon, C. & Small, D. M. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science 322, 449–452 (2008).
Stice, E., Yokum, S., Bohon, C., Marti, N. & Smolen, A. Reward circuitry responsivity to food predicts future increases in body mass: moderating effects of DRD2 and DRD4. Neuroimage 50, 1618–1625 (2010).
Davis, C. et al. Binge eating disorder and the dopamine D2 receptor: genotypes and sub-phenotypes. Prog. Neuropsychopharmacol. Biol. Psychiatry 38, 328–335 (2012).
Carpenter, C. L., Wong, A. M., Li, Z., Noble, E. P. & Heber, D. Association of dopamine D2 receptor and leptin receptor genes with clinically severe obesity. Obesity (Silver Spring) 21, E467–E473 (2013).
Chen, A. L. et al. Correlation of the Taq1 dopamine D2 receptor gene and percent body fat in obese and screened control subjects: a preliminary report. Food Funct. 3, 40–48 (2012).
Comings, D. E., Gade, R., MacMurray, J. P., Muhleman, D. & Peters, W. R. Genetic variants of the human obesity (OB) gene: association with body mass index in young women, psychiatric symptoms, and interaction with the dopamine D2 receptor (DRD2) gene. Mol. Psychiatry 1, 325–335 (1996).
Jenkinson, C. P. et al. Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians. Int. J. Obes. Relat. Metab. Disord. 24, 1233–1238 (2000).
Roth, C. L., Hinney, A., Schur, E. A., Elfers, C. T. & Reinehr, T. Association analyses for dopamine receptor gene polymorphisms and weight status in a longitudinal analysis in obese children before and after lifestyle intervention. BMC Pediatr. 13, 197 (2013).
Ariza, M. et al. Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4–7R) and executive function: their interaction with obesity. PLoS ONE 7, e41482 (2012).
Snyder, S. H. & Pasternak, G. W. Historical review: opioid receptors. Trends Pharmacol. Sci. 24, 198–205 (2003).
Blasio, A., Steardo, L., Sabino, V. & Cottone, P. Opioid system in the medial prefrontal cortex mediates binge-like eating. Addict. Biol. http://dx.doi.org/10.1111/adb.12033 (2013).
Chang, G. Q., Karatayev, O., Barson, J. R., Chang, S. Y. & Leibowitz, S. F. Increased enkephalin in brain of rats prone to overconsuming a fat-rich diet. Physiol. Behav. 101, 360–369 (2010).
Cooper, S. J., Jackson, A. & Kirkham, T. C. Endorphins and food intake: kappa opioid receptor agonists and hyperphagia. Pharmacol. Biochem. Behav. 23, 889–901 (1985).
Kelley, A. E. et al. Opioid modulation of taste hedonics within the ventral striatum. Physiol. Behav. 76, 365–377 (2002).
Kelley, A. E., Will, M. J., Steininger, T. L., Zhang, M. & Haber, S. N. Restricted daily consumption of a highly palatable food (chocolate Ensure®) alters striatal enkephalin gene expression. Eur. J. Neurosci. 18, 2592–2598 (2003).
Zhang, M., Balmadrid, C. & Kelley, A. E. Nucleus accumbens opioid, GABAergic, and dopaminergic modulation of palatable food motivation: contrasting effects revealed by a progressive ratio study in the rat. Behav. Neurosci. 117, 202–211 (2003).
Woolley, J. D., Lee, B. S., Taha, S. A. & Fields, H. L. Nucleus accumbens opioid signaling conditions short-term flavor preferences. Neuroscience 146, 19–30 (2007).
Katsuura, Y. & Taha, S. A. Modulation of feeding and locomotion through mu and delta opioid receptor signaling in the nucleus accumbens. Neuropeptides 44, 225–232 (2010).
Katsuura, Y., Heckmann, J. A. & Taha, S. A. μ-Opioid receptor stimulation in the nucleus accumbens elevates fatty tastant intake by increasing palatability and suppressing satiety signals. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R244–R254 (2011).
Mena, J. D., Sadeghian, K. & Baldo, B. A. Induction of hyperphagia and carbohydrate intake by mu-opioid receptor stimulation in circumscribed regions of frontal cortex. J. Neurosci. 31, 3249–3260 (2011).
Hagan, M. M. & Moss, D. E. An animal model of bulimia nervosa: opioid sensitivity to fasting episodes. Pharmacol. Biochem. Behav. 39, 421–422 (1991).
Boggiano, M. M. et al. Combined dieting and stress evoke exaggerated responses to opioids in binge-eating rats. Behav. Neurosci. 119, 1207–1214 (2005).
Naleid, A. M., Grace, M. K., Chimukangara, M., Billington, C. J. & Levine, A. S. Paraventricular opioids alter intake of high-fat but not high-sucrose diet depending on diet preference in a binge model of feeding. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R99–R105 (2007).
Katsuura, Y. & Taha, S. A. Mu opioid receptor antagonism in the nucleus accumbens shell blocks consumption of a preferred sucrose solution in an anticipatory contrast paradigm. Neuroscience 261, 144–152 (2014).
Rao, R. E., Wojnicki, F. H., Coupland, J., Ghosh, S. & Corwin, R. L. Baclofen, raclopride, and naltrexone differentially reduce solid fat emulsion intake under limited access conditions. Pharmacol. Biochem. Behav. 89, 581–590 (2008).
Giuliano, C., Robbins, T. W., Nathan, P. J., Bullmore, E. T. & Everitt, B. J. Inhibition of opioid transmission at the μ-opioid receptor prevents both food seeking and binge-like eating. Neuropsychopharmacology 37, 2643–2652 (2012).
Lenard, N. R., Zheng, H. & Berthoud, H. R. Chronic suppression of μ-opioid receptor signaling in the nucleus accumbens attenuates development of diet-induced obesity in rats. Int. J. Obes. (Lond.) 34, 1001–1010 (2010).
Shin, A. C., Pistell, P. J., Phifer, C. B. & Berthoud, H. R. Reversible suppression of food reward behavior by chronic mu-opioid receptor antagonism in the nucleus accumbens. Neuroscience 170, 580–588 (2010).
Cottone, P., Sabino, V., Steardo, L. & Zorrilla, E. P. Opioid-dependent anticipatory negative contrast and binge-like eating in rats with limited access to highly preferred food. Neuropsychopharmacology 33, 524–535 (2008).
Yeomans, M. R. & Gray, R. W. Selective effects of naltrexone on food pleasantness and intake. Physiol. Behav. 60, 439–446 (1996).
Yeomans, M. R. & Gray, R. W. Effects of naltrexone on food intake and changes in subjective appetite during eating: evidence for opioid involvement in the appetizer effect. Physiol. Behav. 62, 15–21 (1997).
Bertino, M., Beauchamp, G. K. & Engelman, K. Naltrexone, an opioid blocker, alters taste perception and nutrient intake in humans. Am. J. Physiol. 261, R59–R63 (1991).
Hetherington, M. M., Vervaet, N., Blass, E. & Rolls, B. J. Failure of naltrexone to affect the pleasantness or intake of food. Pharmacol. Biochem. Behav. 40, 185–90 (1991).
Drewnowski, A., Krahn, D. D., Demitrack, M. A., Nairn, K. & Gosnell, B. A. Naloxone, an opiate blocker, reduces the consumption of sweet high-fat foods in obese and lean female binge eaters. Am. J. Clin. Nutr. 61, 1206–1212 (1995).
Mitchell, J. E. et al. A placebo-controlled, double-blind crossover study of naltrexone hydrochloride in outpatients with normal weight bulimia. J. Clin. Psychopharmacol. 9, 94–97 (1989).
Alger, S. A., Schwalberg, M. D., Bigaouette, J. M., Michalek, A. V. & Howard, L. J. Effect of a tricyclic antidepressant and opiate antagonist on binge-eating behavior in normoweight bulimic and obese, binge-eating subjects. Am. J. Clin. Nutr. 53, 865–871 (1991).
Chatoor, I., Herman, B. H. & Hartzler, J. Effects of the opiate antagonist, naltrexone, on binging antecedents and plasma β-endorphin concentrations. J. Am. Acad. Child Adolesc. Psychiatry 33, 748–752 (1994).
Marrazzi, M. A., Bacon, J. P., Kinzie, J. & Luby, E. D. Naltrexone use in the treatment of anorexia nervosa and bulimia nervosa. Int. Clin. Psychopharmacol. 10, 163–172 (1995).
Marrazzi, M. A., Markham, K. M., Kinzie, J. & Luby, E. D. Binge eating disorder: response to naltrexone. Int. J. Obes. Relat. Metab. Disord. 19, 143–145 (1995).
Jonas, J. M. & Gold, M. S. The use of opiate antagonists in treating bulimia: a study of low-dose versus high-dose naltrexone. Psychiatry Res. 24, 195–199 (1988).
Raingeard, I., Courtet, P., Renard, E. & Bringer, J. Naltrexone improves blood glucose control in type 1 diabetic women with severe and chronic eating disorders. Diabetes Care 27, 847–848 (2004).
Neumeister, A., Winkler, A. & Wober-Bingol, C. Addition of naltrexone to fluoxetine in the treatment of binge eating disorder. Am. J. Psychiatry 156, 797 (1999).
Daubenmier, J. et al. A new biomarker of hedonic eating? A preliminary investigation of cortisol and nausea responses to acute opioid blockade. Appetite 74, 92–100 (2014).
McElroy, S. L. et al. A placebo-controlled pilot study of the novel opioid receptor antagonist ALKS-33 in binge eating disorder. Int. J. Eat. Disord. 46, 239–245 (2013).
Davis, C. et al. Opiates, overeating and obesity: a psychogenetic analysis. Int. J. Obes. (Lond.) 35, 1347–1354 (2011).
Haghighi, A. et al. Opioid receptor μ 1 gene, fat intake and obesity in adolescence. Mol. Psychiatry 19, 63–68 (2014).
Davis, C. A. et al. Dopamine for “wanting” and opioids for “liking”: a comparison of obese adults with and without binge eating. Obesity (Silver Spring) 17, 1220–1225 (2009).
Hatsukami, D., Owen, P., Pyle, R. & Mitchell, J. Similarities and differences on the MMPI between women with bulimia and women with alcohol or drug abuse problems. Addict. Behav. 7, 435–439 (1982).
Leon, G. R., Kolotkin, R. & Korgeski, G. MacAndrew Addiction Scale and other MMPI characteristics associated with obesity, anorexia and smoking behavior. Addict. Behav. 4, 401–407 (1979).
Scott, D. W. Alcohol and food abuse: some comparisons. Br. J. Addict. 78, 339–349 (1983).
Tuomisto, T. et al. Psychological and physiological characteristics of sweet food “addiction”. Int. J. Eat. Disord. 25, 169–175 (1999).
Cassin, S. E. & von Ranson, K. M. Is binge eating experienced as an addiction? Appetite 49, 687–690 (2007).
Goodman, A. Addiction: definition and implications. Br. J. Addict. 85, 1403–1408 (1990).
Curtis, C. & Davis, C. A qualitative study of binge eating and obesity from an addiction perspective. Eat. Disord. 22, 19–32 (2014).
Lent, M. R. & Swencionis, C. Addictive personality and maladaptive eating behaviors in adults seeking bariatric surgery. Eat. Behav. 13, 67–70 (2012).
Davis, C. et al. 'Food addiction' and its association with a dopaminergic multilocus genetic profile. Physiol. Behav. 118, 63–69 (2013).
Burmeister, J. M., Hinman, N., Koball, A., Hoffmann, D. A. & Carels, R. A. Food addiction in adults seeking weight loss treatment. Implications for psychosocial health and weight loss. Appetite 60, 103–110 (2013).
Gearhardt, A. N. et al. Neural correlates of food addiction. Arch. Gen. Psychiatry 68, 808–816 (2011).
Meule, A. Food addiction and body-mass-index: a non-linear relationship. Med. Hypotheses 79, 508–511 (2012).
Eichen, D. M., Lent, M. R., Goldbacher, E. & Foster, G. D. Exploration of “food addiction” in overweight and obese treatment-seeking adults. Appetite 67, 22–24 (2013).
Gearhardt, A. N., Roberto, C. A., Seamans, M. J., Corbin, W. R. & Brownell, K. D. Preliminary validation of the Yale Food Addiction Scale for children. Eat. Behav. 14, 508–512 (2013).
Mason, S. M., Flint, A. J., Field, A. E., Austin, S. B. & Rich-Edwards, J. W. Abuse victimization in childhood or adolescence and risk of food addiction in adult women. Obesity (Silver Spring) 21, E775–E781 (2013).
Meule, A., Lutz, A., Vögele, C. & Kübler, A. Women with elevated food addiction symptoms show accelerated reactions, but no impaired inhibitory control, in response to pictures of high-calorie food-cues. Eat. Behav. 13, 423–428 (2012).
Murphy, C. M., Stojek, M. K. & MacKillop, J. Interrelationships among impulsive personality traits, food addiction, and body mass index. Appetite 73, 45–50 (2014).
Gearhardt, A. N., White, M. A., Masheb, R. M. & Grilo, C. M. An examination of food addiction in a racially diverse sample of obese patients with binge eating disorder in primary care settings. Compr. Psychiatry 54, 500–505 (2013).
Meule, A. & Kübler, A. Food cravings in food addiction: the distinct role of positive reinforcement. Eat. Behav. 13, 252–255 (2012).
Bégin C. et al. Does food addiction distinguish a specific subgroup of overweight/obese overeating women? Health 4, 1492–1499 (2012).
Berridge, K. C., Robinson, T. E. & Aldridge, J. W. Dissecting components of reward: 'liking', 'wanting', and learning. Curr. Opin. Pharmacol. 9, 65–73 (2009).
Lent, M. R., Eichen, D. M., Goldbacher, E., Wadden, T. A. & Foster, G. D. Relationship of food addiction to weight loss and attrition during obesity treatment. Obesity (Silver Spring) 22, 52–55 (2014).
Ziauddeen, H. & Fletcher, P. C. Is food addiction a valid and useful concept? Obes. Rev. 14, 19–28 (2013).
Clark, S. M. & Saules, K. K. Validation of the Yale Food Addiction Scale among a weight-loss surgery population. Eat. Behav. 14, 216–219 (2013).
Meule, A., Heckel, D. & Kübler, A. Factor structure and item analysis of the Yale Food Addiction Scale in obese candidates for bariatric surgery. Eur. Eat. Disord. Rev. 20, 419–422 (2012).
Gearhardt, A. N., Corbin, W. R. & Brownell, K. D. Preliminary validation of the Yale Food Addiction Scale. Appetite 52, 430–436 (2009).
Meule, A., Vögele, C. & Kübler, A. German Translation and Validation of the Yale Food Addiction Scale [German]. Diagnostica 58, 115–126 (2012).
Flint, A. J. et al. Food addiction scale measurement in 2 cohorts of middle-aged and older women. Am. J. Clin. Nutr. 99, 578–586 (2014).
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S.M. and A.T. researched data for the Review. S.M., A.T. and N.M.A. were involved in the writing of the paper. All authors contributed to the review and editing of the manuscript.
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Murray, S., Tulloch, A., Gold, M. et al. Hormonal and neural mechanisms of food reward, eating behaviour and obesity. Nat Rev Endocrinol 10, 540–552 (2014). https://doi.org/10.1038/nrendo.2014.91
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DOI: https://doi.org/10.1038/nrendo.2014.91
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