Abstract
The growing rates of obesity have prompted comparisons between the uncontrolled intake of food and drugs; however, an evaluation of the equivalence of food- and drug-related behaviors requires a thorough understanding of the underlying neural circuits driving each behavior. Although it has been attractive to borrow neurobiological concepts from addiction to explore compulsive food seeking, a more integrated model is needed to understand how food and drugs differ in their ability to drive behavior. In this Review, we will examine the commonalities and differences in the systems-level and behavioral responses to food and to drugs of abuse, with the goal of identifying areas of research that would address gaps in our understanding and ultimately identify new treatments for obesity or drug addiction.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kenny, P.J. Common cellular and molecular mechanisms in obesity and drug addiction. Nat. Rev. Neurosci. 12, 638–651 (2011).
Ziauddeen, H., Farooqi, I.S. & Fletcher, P.C. Obesity and the brain: how convincing is the addiction model? Nat. Rev. Neurosci. 13, 279–286 10.1038/nrn3212 (2012).
Baldo, B.A. & Kelley, A.E. Discrete neurochemical coding of distinguishable motivational processes: insights from nucleus accumbens control of feeding. Psychopharmacology (Berl.) 191, 439–459 (2007).
Horvath, T.L. & Diano, S. The floating blueprint of hypothalamic feeding circuits. Nat. Rev. Neurosci. 5, 662–667 (2004).
van den Pol, A.N. Weighing the role of hypothalamic feeding neurotransmitters. Neuron 40, 1059–1061 (2003).
Koob, G.F. Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol. Sci. 13, 177–184 (1992).
Schultz, W. Behavioral dopamine signals. Trends Neurosci. 30, 203–210 (2007).
Wise, R.A., Spindler, J. & Legault, L. Major attenuation of food reward with performance-sparing doses of pimozide in the rat. Can. J. Psychol. 32, 77–85 (1978).
Wise, R.A. Role of brain dopamine in food reward and reinforcement. Phil. Trans. R. Soc. Lond. B 361, 1149–1158 (2006).
Wise, R.A. Dopamine, learning and motivation. Nat. Rev. Neurosci. 5, 483–494 (2004).
Berridge, K.C. The debate over dopamine's role in reward: the case for incentive salience. Psychopharmacology (Berl.) 191, 391–431 (2007).
Salamone, J.D., Mahan, K. & Rogers, S. Ventrolateral striatal dopamine depletions impair feeding and food handling in rats. Pharmacol. Biochem. Behav. 44, 605–610 (1993).
Baldo, B.A., Sadeghian, K., Basso, A.M. & Kelley, A.E. Effects of selective dopamine D1 or D2 receptor blockade within nucleus accumbens subregions on ingestive behavior and associated motor activity. Behav. Brain Res. 137, 165–177 (2002).
Palmiter, R.D. Is dopamine a physiologically relevant mediator of feeding behavior? Trends Neurosci. 30, 375–381 (2007).
Zhou, Q.Y. & Palmiter, R.D. Dopamine-deficient mice are severely hypoactive, adipsic, and aphagic. Cell 83, 1197–1209 (1995).
Cannon, C.M. & Palmiter, R.D. Reward without dopamine. J. Neurosci. 23, 10827–10831 (2003).
Kelley, A.E., Baldo, B.A., Pratt, W.E. & Will, M.J. Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward. Physiol. Behav. 86, 773–795 (2005).
Aponte, Y., Atasoy, D. & Sternson, S.M. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat. Neurosci. 14, 351–355 (2011).
Schwartz, G.J. The role of gastrointestinal vagal afferents in the control of food intake: current prospects. Nutrition 16, 866–873 (2000).
Goeders, N.E. Stress and cocaine addiction. J. Pharmacol. Exp. Ther. 301, 785–789 (2002).
Dar, R. & Frenk, H. Do smokers self-administer pure nicotine? A review of the evidence. Psychopharmacology (Berl.) 173, 18–26 (2004).
Gray, M.A. & Critchley, H.D. Interoceptive basis to craving. Neuron 54, 183–186 (2007).
Hommel, J.D. et al. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51, 801–810 (2006).
Fulton, S. et al. Leptin regulation of the mesoaccumbens dopamine pathway. Neuron 51, 811–822 (2006).
DiLeone, R.J., Georgescu, D. & Nestler, E.J. Lateral hypothalamic neuropeptides in reward and drug addiction. Life Sci. 73, 759–768 (2003).
Havel, P.J. Peripheral signals conveying metabolic information to the brain: short-term and long-term regulation of food intake and energy homeostasis. Exp. Biol. Med. (Maywood) 226, 963–977 (2001).
Ren, X. et al. Nutrient selection in the absence of taste receptor signaling. J. Neurosci. 30, 8012–8023 (2010).
Fowler, C.D., Lu, Q., Johnson, P.M., Marks, M.J. & Kenny, P.J. Habenular alpha5 nicotinic receptor subunit signalling controls nicotine intake. Nature 471, 597–601 (2011).
Frahm, S. et al. Aversion to nicotine is regulated by the balanced activity of beta4 and alpha5 nicotinic receptor subunits in the medial habenula. Neuron 70, 522–535 (2011).
Koob, G.F. Animal models of drug addiction. in Psychopharmacology: The Fourth Generation of Progress (eds. Bloom, F.E. & Kupfer, D.J.) 759–772 (Lippincott Williams & Wilkins, 1995).
Wheeler, R.A. et al. Cocaine cues drive opposing context-dependent shifts in reward processing and emotional state. Biol. Psychiatry 69, 1067–1074 (2011).
Wise, R.A. & Kiyatkin, E.A. Differentiating the rapid actions of cocaine. Nat. Rev. Neurosci. 12, 479–484 (2011).
Ahmed, S.H. & Koob, G.F. Transition from moderate to excessive drug intake: change in hedonic set point. Science 282, 298–300 (1998).
Wu, Q., Boyle, M.P. & Palmiter, R.D. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell 137, 1225–1234 (2009).
Yamamoto, T. Brain regions responsible for the expression of conditioned taste aversion in rats. Chem. Senses 32, 105–109 (2007).
Stark, R. et al. Erotic and disgust-inducing pictures–differences in the hemodynamic responses of the brain. Biol. Psychol. 70, 19–29 (2005).
Wright, C. & Moore, R.D. Disulfiram treatment of alcoholism. Am. J. Med. 88, 647–655 (1990).
Sorensen, L.B., Moller, P., Flint, A., Martens, M. & Raben, A. Effect of sensory perception of foods on appetite and food intake: a review of studies on humans. Int. J. Obes. Relat. Metab. Disord. 27, 1152–1166 (2003).
Stewart, J., de Wit, H. & Eikelboom, R. Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants. Psychol. Rev. 91, 251–268 (1984).
Seymour, B. Carry on eating: neural pathways mediating conditioned potentiation of feeding. J. Neurosci. 26, 1061–1062 discussion 1062 (2006).
Singh, A. et al. Leptin-mediated changes in hepatic mitochondrial metabolism, structure, and protein levels. Proc. Natl. Acad. Sci. USA 106, 13100–13105 (2009).
Everitt, B.J. & Robbins, T.W. Neural systems of reinforcement for drug addiction: from actions to habits to compulsion. Nat. Neurosci. 8, 1481–1489 (2005).
Dalley, J.W., Everitt, B.J. & Robbins, T.W. Impulsivity, compulsivity, and top-down cognitive control. Neuron 69, 680–694 (2011).
Jentsch, J.D. & Taylor, J.R. Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology (Berl.) 146, 373–390 (1999).
Davidson, T.L. et al. Contributions of the hippocampus and medial prefrontal cortex to energy and body weight regulation. Hippocampus 19, 235–252 (2009).
Grakalic, I., Panlilio, L.V., Quiroz, C. & Schindler, C.W. Effects of orbitofrontal cortex lesions on cocaine self-administration. Neuroscience 165, 313–324 (2010).
Kalivas, P.W., Volkow, N. & Seamans, J. Unmanageable motivation in addiction: a pathology in prefrontal-accumbens glutamate transmission. Neuron 45, 647–650 (2005).
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).
Vucetic, Z., Kimmel, J. & Reyes, T.M. Chronic high-fat diet drives postnatal epigenetic regulation of mu-opioid receptor in the brain. Neuropsychopharmacology 36, 1199–1206 (2011).
Guegan, T. et al. Operant behavior to obtain palatable food modifies ERK activity in the brain reward circuit. Eur. Neuropsychopharmacol. 10.1016/j.euroneuro.2012.04.009 (2012).
Guegan, T. et al. Operant behavior to obtain palatable food modifies neuronal plasticity in the brain reward circuit. Eur. Neuropsychopharmacol. 10.1016/j.euroneuro.2012.04.004 (2012).
Small, D.M., Veldhuizen, M.G., Felsted, J., Mak, Y.E. & McGlone, F. Separable substrates for anticipatory and consummatory food chemosensation. Neuron 57, 786–797 (2008).
Piguet, O. Eating disturbance in behavioural-variant frontotemporal dementia. J. Mol. Neurosci. 45, 589–593 (2011).
Kyrkouli, S.E., Stanley, B.G., Seirafi, R.D. & Leibowitz, S.F. Stimulation of feeding by galanin: anatomical localization and behavioral specificity of this peptide's effects in the brain. Peptides 11, 995–1001 (1990).
Stanley, B.G. & Leibowitz, S.F. Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proc. Natl. Acad. Sci. USA 82, 3940–3943 (1985).
Maric, T., Cantor, A., Cuccioletta, H., Tobin, S. & Shalev, U. Neuropeptide Y augments cocaine self-administration and cocaine-induced hyperlocomotion in rats. Peptides 30, 721–726 (2009).
Narasimhaiah, R., Kamens, H.M. & Picciotto, M.R. Effects of galanin on cocaine-mediated conditioned place preference and ERK signaling in mice. Psychopharmacology (Berl.) 204, 95–102 (2009).
Hsu, R. et al. Blockade of melanocortin transmission inhibits cocaine reward. Eur. J. Neurosci. 21, 2233–2242 (2005).
Benoit, S.C. et al. A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci. 20, 3442–3448 (2000).
Löf, E., Olausson, P., Stomberg, R., Taylor, J.R. & Soderpalm, B. Nicotinic acetylcholine receptors are required for the conditioned reinforcing properties of sucrose-associated cues. Psychopharmacology (Berl.) 212, 321–328 (2010).
Mineur, Y.S. et al. Nicotine decreases food intake through activation of POMC neurons. Science 332, 1330–1332 (2011).
Zhang, M., Gosnell, B.A. & Kelley, A.E. Intake of high-fat food is selectively enhanced by mu opioid receptor stimulation within the nucleus accumbens. J. Pharmacol. Exp. Ther. 285, 908–914 (1998).
Brabant, C., Kuschpel, A.S. & Picciotto, M.R. Locomotion and self-administration induced by cocaine in 129/OlaHsd mice lacking galanin. Behav. Neurosci. 124, 828–838 (2010).
Lenoir, M., Serre, F., Cantin, L. & Ahmed, S.H. Intense sweetness surpasses cocaine reward. PLoS ONE 2, e698 (2007).
Avena, N.M. & Hoebel, B.G. A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine. Neuroscience 122, 17–20 (2003).
Kearns, D.N., Gomez-Serrano, M.A. & Tunstall, B.J. A review of preclinical research demonstrating that drug and non-drug reinforcers differentially affect behavior. Curr. Drug Abuse Rev. 4, 261–269 (2011).
Pickens, C.L. et al. Effect of fenfluramine on reinstatement of food seeking in female and male rats: implications for the predictive validity of the reinstatement model. Psychopharmacology (Berl.) 221, 341–353 (2012).
Lu, L., Grimm, J.W., Hope, B.T. & Shaham, Y. Incubation of cocaine craving after withdrawal: a review of preclinical data. Neuropharmacology 47 (suppl. 1) 214–226 (2004).
Ahmed, S.H. & Koob, G.F. Cocaine- but not food-seeking behavior is reinstated by stress after extinction. Psychopharmacology (Berl.) 132, 289–295 (1997).
Nair, S.G., Gray, S.M. & Ghitza, U.E. Role of food type in yohimbine- and pellet-priming-induced reinstatement of food seeking. Physiol. Behav. 88, 559–566 (2006).
Troop, N.A. & Treasure, J.L. Psychosocial factors in the onset of eating disorders: responses to life-events and difficulties. Br. J. Med. Psychol. 70, 373–385 (1997).
Blanchard, D.C. et al. Visible burrow system as a model of chronic social stress: behavioral and neuroendocrine correlates. Psychoneuroendocrinology 20, 117–134 (1995).
Dulawa, S.C. & Hen, R. Recent advances in animal models of chronic antidepressant effects: the novelty-induced hypophagia test. Neurosci. Biobehav. Rev. 29, 771–783 (2005).
Smagin, G.N., Howell, L.A., Redmann, S. Jr., Ryan, D.H. & Harris, R.B. Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist. Am. J. Physiol. 276, R1461–R1468 (1999).
Torregrossa, M.M., Quinn, J.J. & Taylor, J.R. Impulsivity, compulsivity, and habit: the role of orbitofrontal cortex revisited. Biol. Psychiatry 63, 253–255 (2008).
Pierce, R.C. & Vanderschuren, L.J. Kicking the habit: the neural basis of ingrained behaviors in cocaine addiction. Neurosci. Biobehav. Rev. 35, 212–219 (2010).
Belin, D. & Everitt, B.J. Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum. Neuron 57, 432–441 (2008).
Zapata, A., Minney, V.L. & Shippenberg, T.S. Shift from goal-directed to habitual cocaine seeking after prolonged experience in rats. J. Neurosci. 30, 15457–15463 (2010).
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).
Forlano, P.M. & Cone, R.D. Conserved neurochemical pathways involved in hypothalamic control of energy homeostasis. J. Comp. Neurol. 505, 235–248 (2007).
Gearhardt, A.N., Corbin, W.R. & Brownell, K.D. Food addiction: an examination of the diagnostic criteria for dependence. J. Addict. Med. 3, 1–7 (2009).
DiLeone, R.J., Georgescu, D. & Nestler, E.J. Lateral hypothalamic neuropeptides in reward and drug addiction. Life Sci. 73, 759–768 (2003).
Shalev, U., Yap, J. & Shaham, Y. Leptin attenuates acute food deprivation-induced relapse to heroin seeking. J. Neurosci. 21, RC129 (2001).
Smith, R.J., Tahsili-Fahadan, P. & Aston-Jones, G. Orexin/hypocretin is necessary for context-driven cocaine-seeking. Neuropharmacology 58, 179–184 (2010).
Shiraishi, T., Oomura, Y., Sasaki, K. & Wayner, M.J. Effects of leptin and orexin-A on food intake and feeding related hypothalamic neurons. Physiol. Behav. 71, 251–261 (2000).
Edwards, C.M. et al. The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin. J. Endocrinol. 160, R7–R12 (1999).
Chung, S. et al. The melanin-concentrating hormone system modulates cocaine reward. Proc. Natl. Acad. Sci. USA 106, 6772–6777 (2009).
Boules, M. et al. The neurotensin receptor agonist NT69L suppresses sucrose-reinforced operant behavior in the rat. Brain Res. 1127, 90–98 (2007).
Richelson, E., Boules, M. & Fredrickson, P. Neurotensin agonists: possible drugs for treatment of psychostimulant abuse. Life Sci. 73, 679–690 (2003).
Hunter, R.G. & Kuhar, M.J. CART peptides as targets for CNS drug development. Curr. Drug Targets CNS Neurol. Disord. 2, 201–205 (2003).
Jerlhag, E., Egecioglu, E., Dickson, S.L. & Engel, J.A. Ghrelin receptor antagonism attenuates cocaine- and amphetamine-induced locomotor stimulation, accumbal dopamine release, and conditioned place preference. Psychopharmacology (Berl.) 211, 415–422 (2010).
Abizaid, A. et al. Reduced locomotor responses to cocaine in ghrelin-deficient mice. Neuroscience 192, 500–506 (2011).
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).
Acknowledgements
This work was supported by US National Institutes of Health grants DK076964 (R.J.D.), DA011017 (J.R.T.), DA015222 (J.R.T.), DA15425 (M.R.P.) and DA014241 (M.R.P.).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
DiLeone, R., Taylor, J. & Picciotto, M. The drive to eat: comparisons and distinctions between mechanisms of food reward and drug addiction. Nat Neurosci 15, 1330–1335 (2012). https://doi.org/10.1038/nn.3202
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn.3202
This article is cited by
-
Exploring the association between circRNA expression and pediatric obesity based on a case–control study and related bioinformatics analysis
BMC Pediatrics (2023)
-
A limited and intermittent access to a high-fat diet modulates the effects of cocaine-induced reinstatement in the conditioned place preference in male and female mice
Psychopharmacology (2021)
-
Bacteroides uniformis CECT 7771 Modulates the Brain Reward Response to Reduce Binge Eating and Anxiety-Like Behavior in Rat
Molecular Neurobiology (2021)
-
Brain–gut–microbiome interactions in obesity and food addiction
Nature Reviews Gastroenterology & Hepatology (2020)
-
Dopamine in the oval bed nucleus of the stria terminalis contributes to compulsive responding for sucrose in rats
Neuropsychopharmacology (2019)