Abstract
Reward sensitivity and possible alterations in the dopaminergic-reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food-reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (body mass index (BMI)=27.0 kg/m2 ±4.79 SD; age=28 years ±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a ‘wanting’ and ‘liking’ rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of BMI. Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward, and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food-reward processing. This effect is, however, independent of BMI, which contradicts the reward-deficiency hypothesis. This hints to the hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Alonso-Alonso M, Woods SC, Pelchat M, Grigson PS, Stice E, Farooqi S et al (2015). Food reward system: current perspectives and future research needs. Nutr Rev 73: 296–307.
Batterink L, Yokum S, Stice E (2010). Body mass correlates inversely with inhibitory control in response to food among adolescent girls: an fMRI study. Neuroimage 52: 1696–1703.
Beeler JA, Frazier CR, Zhuang X (2012). Dopaminergic enhancement of local food-seeking is under global homeostatic control. Eur J Neurosci 35: 146–159.
Berridge KC (1996). Food reward: brain substrates of wanting and liking. Neurosci Biobehav Rev 20: 1–25.
Berridge KC (2009). 'Liking' and 'wanting' food rewards: brain substrates and roles in eating disorders. Physiol Behav 97: 537–550.
Bjork JM, Grant SJ, Chen G, Hommer DW (2013). Dietary tyrosine/phenylalanine depletion effects on behavioral and brain signatures of human motivational processing. Neuropsychopharmacology 39: 595–604.
Blum K, Thanos PK, Gold MS (2014). Dopamine and glucose, obesity, and reward deficiency syndrome. Front Psychol 5: 919.
Booij L, Van der Does AJ, Riedel WJ (2003). Monoamine depletion in psychiatric and healthy populations: review. Mol Psychiatry 8: 951–973.
Bosak K, Martin L (2014). Neuroimaging of goal-directed behavior in midlife women. Nurs Res 63: 388–396.
Burger KS, Stice E (2011). Variability in reward responsivity and obesity: evidence from brain imaging studies. Curr Drug Abuse Rev 4: 182–189.
Burger KS, Stice E (2013). Elevated energy intake is correlated with hyperresponsivity in attentional, gustatory, and reward brain regions while anticipating palatable food receipt. Am J Clin Nutr 97: 1188–1194.
Carnell S, Gibson C, Benson L, Ochner CN, Geliebter A (2012). Neuroimaging and obesity: current knowledge and future directions. Obes Rev 13: 43–56.
Cools R, D'Esposito M (2011). Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry 69: e113–e125.
Coull JT, Hwang HJ, Leyton M, Dagher A (2012). Dopamine precursor depletion impairs timing in healthy volunteers by attenuating activity in putamen and supplementary motor area. J Neurosci 32: 16704–16715.
Dagher A (2012). Functional brain imaging of appetite. Trends Endocrinol Metab 23: 250–260.
Dambacher F, Sack AT, Lobbestael J, Arntz A, Brugmann S, Schuhmann T (2014). The role of right prefrontal and medial cortex in response inhibition: interfering with action restraint and action cancellation using transcranial magnetic brain stimulation. J Cogn Neurosci 26: 1775–1784.
Davis C, Strachan S, Berkson M (2004). Sensitivity to reward: implications for overeating and overweight. Appetite 42: 131–138.
de Wit S, Standing HR, Devito EE, Robinson OJ, Ridderinkhof KR, Robbins TW et al (2012). Reliance on habits at the expense of goal-directed control following dopamine precursor depletion. Psychopharmacology 219: 621–631.
Ellis KA, Mehta MA, Naga Venkatesha Murthy PJ, McTavish SF, Nathan PJ, Grasby PM (2007). Tyrosine depletion alters cortical and limbic blood flow but does not modulate spatial working memory performance or task-related blood flow in humans. Hum Brain Mapp 28: 1136–1149.
Feld GB, Besedovsky L, Kaida K, Munte TF, Born J (2014). Dopamine D2-like receptor activation wipes out preferential consolidation of high over low reward memories during human sleep. J Cogn Neurosci 26: 2310–2320.
Fernstrom JD, Fernstrom MH (1994). Dietary effects on tyrosine availability and catecholamine synthesis in the central nervous system: possible relevance to the control of protein intake. Proc Nutr Soc 53: 419–429.
Finlayson G, King N, Blundell JE (2007). Liking vs. wanting food: importance for human appetite control and weight regulation. Neurosci Biobehav Rev 31: 987–1002.
Fitzpatrick S, Gilbert S, Serpell L (2013). Systematic review: are overweight and obese individuals impaired on behavioural tasks of executive functioning? Neuropsychol Rev 23: 138–156.
Garland T Jr, Schutz H, Chappell MA, Keeney BK, Meek TH, Copes LE et al (2011). The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives. J Exp Biol 214 (Pt 2): 206–229.
Goldberg II, Harel M, Malach R (2006). When the brain loses its self: prefrontal inactivation during sensorimotor processing. Neuron 50: 329–339.
Hardman CA, Herbert VM, Brunstrom JM, Munafo MR, Rogers PJ (2012). Dopamine and food reward: effects of acute tyrosine/phenylalanine depletion on appetite. Physiol Behav 105: 1202–1207.
Hege MA, Stingl KT, Ketterer C, Haring HU, Heni M, Fritsche A et al (2013). Working memory-related brain activity is associated with outcome of lifestyle intervention. Obesity 21: 2488–2494.
Hilbert A, Tuschen-Caffier B, Karwautz A, Niederhofer H, Munsch S (2007). Eating disorder examination-questionnaire: psychometric properties of the German version. Diagnostica 53: 144–154.
Hitsman B, MacKillop J, Lingford-Hughes A, Williams TM, Ahmad F, Adams S et al (2008). Effects of acute tyrosine/phenylalanine depletion on the selective processing of smoking-related cues and the relative value of cigarettes in smokers. Psychopharmacology 196: 611–621.
Ito H, Kodaka F, Takahashi H, Takano H, Arakawa R, Shimada H et al (2011). Relation between presynaptic and postsynaptic dopaminergic functions measured by positron emission tomography: implication of dopaminergic tone. J Neurosci 31: 7886–7890.
Karlsson HK, Tuominen L, Tuulari JJ, Hirvonen J, Parkkola R, Helin S et al (2015). Obesity is associated with decreased mu-opioid but unaltered dopamine D2 receptor availability in the brain. J Neurosci 35: 3959–3965.
Kenny PJ (2011). Reward mechanisms in obesity: new insights and future directions. Neuron 69: 664–679.
Kullmann S, Pape AA, Heni M, Ketterer C, Schick F, Haring HU et al (2013). Functional network connectivity underlying food processing: disturbed salience and visual processing in overweight and obese adults. Cereb Cortex 23: 1247–1256.
Leyton M, Boileau I, Benkelfat C, Diksic M, Baker G, Dagher A (2002). Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: a PET/[11C]raclopride study in healthy men. Neuropsychopharmacology 27: 1027–1035.
Leyton M, Casey KF, Delaney JS, Kolivakis T, Benkelfat C (2005). Cocaine craving, euphoria, and self-administration: a preliminary study of the effect of catecholamine precursor depletion. Behav Neurosci 119: 1619–1627.
Leyton M, Dagher A, Boileau I, Casey K, Baker GB, Diksic M et al (2004). Decreasing amphetamine-induced dopamine release by acute phenylalanine/tyrosine depletion: a PET/[11C]raclopride study in healthy men. Neuropsychopharmacology 29: 427–432.
Leyton M, Young SN, Blier P, Baker GB, Pihl RO, Benkelfat C (2000). Acute tyrosine depletion and alcohol ingestion in healthy women. Alcohol Clin Exp Res 24: 459–464.
Lowe MR, Butryn ML (2007). Hedonic hunger: a new dimension of appetite? Physiol Behav 91: 432–439.
McTavish SF, Cowen PJ, Sharp T (1999a). Effect of a tyrosine-free amino acid mixture on regional brain catecholamine synthesis and release. Psychopharmacology 141: 182–188.
McTavish SF, McPherson MH, Sharp T, Cowen PJ (1999b). Attenuation of some subjective effects of amphetamine following tyrosine depletion. J Psychopharmacol 13: 144–147.
Medic N, Ziauddeen H, Vestergaard MD, Henning E, Schultz W, Farooqi IS et al (2014). Dopamine modulates the neural representation of subjective value of food in hungry subjects. J Neurosci 34: 16856–16864.
Montgomery AJ, McTavish SF, Cowen PJ, Grasby PM (2003). Reduction of brain dopamine concentration with dietary tyrosine plus phenylalanine depletion: an [11C]raclopride PET study. Am J Psychiatry 160: 1887–1889.
Munafo MR, Mannie ZN, Cowen PJ, Harmer CJ, McTavish SB (2007). Effects of acute tyrosine depletion on subjective craving and selective processing of smoking-related cues in abstinent cigarette smokers. J Psychopharmacol 21: 805–814.
Nagano-Saito A, Cisek P, Perna AS, Shirdel FZ, Benkelfat C, Leyton M et al (2012). From anticipation to action, the role of dopamine in perceptual decision making: an fMRI-tyrosine depletion study. J Neurophysiol 108: 501–512.
Nagano-Saito A, Leyton M, Monchi O, Goldberg YK, He Y, Dagher A (2008). Dopamine depletion impairs frontostriatal functional connectivity during a set-shifting task. J Neurosci 28: 3697–3706.
Ninan I, Kulkarni SK (1998). Dopamine receptor sensitive effect of dizocilpine on feeding behaviour. Brain Res 812: 157–163.
Pudel D, Westenhöfer J (1989) Fragebogen zum Eßverhalten (FEV). Handanweisung. Hogrefe: Göttingen.
Richard JM, Castro DC, Difeliceantonio AG, Robinson MJ, Berridge KC (2012). Mapping brain circuits of reward and motivation: in the footsteps of Ann Kelley. Neurosci Biobehav Rev 37 (9 Pt A): 1919–1931.
Robinson OJ, Standing HR, DeVito EE, Cools R, Sahakian BJ (2010). Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males. Psychopharmacology 211: 187–195.
Salamone JD, Steinpreis RE, McCullough LD, Smith P, Grebel D, Mahan K (1991). Haloperidol and nucleus accumbens dopamine depletion suppress lever pressing for food but increase free food consumption in a novel food choice procedure. Psychopharmacology 104: 515–521.
Scharmuller W, Ubel S, Ebner F, Schienle A (2012). Appetite regulation during food cue exposure: a comparison of normal-weight and obese women. Neurosci Lett 518: 106–110.
Shohamy D, Adcock RA (2010). Dopamine and adaptive memory. Trends Cogn Sci 14: 464–472.
Simon JJ, Skunde M, Wu M, Schnell K, Herpertz SC, Bendszus M et al (2014). Neural dissociation of food- and money-related reward processing using an abstract incentive delay task. Soc Cogn Affect Neurosci 10: 1113–1120.
Smith E, Hay P, Campbell L, Trollor JN (2011). A review of the association between obesity and cognitive function across the lifespan: implications for novel approaches to prevention and treatment. Obes Rev 12: 740–755.
Stice E, Burger KS, Yokum S (2015). Reward region responsivity predicts future weight gain and moderating effects of the TaqIA allele. J Neurosci 35: 10316–10324.
Stice E, Spoor S, Bohon C, Small DM (2008). Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science 322: 449–452.
Stice E, Yokum S, Burger K, Epstein L, Smolen A (2012). Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity. J Neurosci 32: 10093–10100.
Stice E, Yokum S, Burger KS, Epstein LH, Small DM (2011). Youth at risk for obesity show greater activation of striatal and somatosensory regions to food. J Neurosci 31: 4360–4366.
Stingl KT, Kullmann S, Ketterer C, Heni M, Haring HU, Fritsche A et al (2012). Neuronal correlates of reduced memory performance in overweight subjects. Neuroimage 60: 362–369.
Stoeckel LE, Weller RE, Cook EW III, Twieg DB, Knowlton RC, Cox JE (2008). Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage 41: 636–647.
Sui J, Chechlacz M, Humphreys GW (2012). Dividing the self: distinct neural substrates of task-based and automatic self-prioritization after brain damage. Cognition 122: 150–162.
Tellez LA, Medina S, Han W, Ferreira JG, Licona-Limon P, Ren X et al (2013). A gut lipid messenger links excess dietary fat to dopamine deficiency. Science 341: 800–802.
van Zessen R, van der Plasse G, Adan RA (2012). Contribution of the mesolimbic dopamine system in mediating the effects of leptin and ghrelin on feeding. Proc Nutr Soc 71: 435–445.
Venugopalan VV, Casey KF, O'Hara C, O'Loughlin J, Benkelfat C, Fellows LK et al (2011). Acute phenylalanine/tyrosine depletion reduces motivation to smoke cigarettes across stages of addiction. Neuropsychopharmacology 36: 2469–2476.
Volkow ND, Wang GJ, Baler RD (2011). Reward, dopamine and the control of food intake: implications for obesity. Trends Cogn Sci 15: 37–46.
Volkow ND, Wang GJ, Tomasi D, Baler RD (2012). Obesity and addiction: neurobiological overlaps. Obes Rev 14: 2–18.
Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W et al (2001). Brain dopamine and obesity. Lancet 357: 354–357.
Woo CW, Krishnan A, Wager TD (2014). Cluster-extent based thresholding in fMRI analyses: pitfalls and recommendations. Neuroimage 91: 412–419.
Acknowledgements
We thank Maike Borutta very much for her assistance during the measurements, Hubert Kalbacher for his advice regarding the amino acid analyses and Shirley Würth for language editing and proofreading of the manuscript.
Author contributions
Study design: AF, H-CF, HP, HS, PE, and SF; material/test preparation: HS, RV, PE, SF, TU, and U-MB; pilot study: AF, HP, HS, KL, MH, RV, SF, and TU; data acquisition: KL, MH, RV, SF, TU, and U-MB; blood sampling and sample preparation: KL, MH, TU, and U-MB; data analyses: KL, MH, RV, and SF; manuscript preparation: RV and SF; interpretation of the results: AF, H-CF, HP, MH, PE, RV, and SF; and manuscript revision and approval: all authors.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on the Neuropsychopharmacology website
Supplementary information
Rights and permissions
About this article
Cite this article
Frank, S., Veit, R., Sauer, H. et al. Dopamine Depletion Reduces Food-Related Reward Activity Independent of BMI. Neuropsychopharmacol 41, 1551–1559 (2016). https://doi.org/10.1038/npp.2015.313
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/npp.2015.313
This article is cited by
-
Changes in Food Preferences Before and After Intragastric Balloon Placement
Obesity Surgery (2024)
-
Neural Correlates of Impaired Reward–Effort Integration in Remitted Bulimia Nervosa
Neuropsychopharmacology (2018)
-
Oxytocin curbs calorie intake via food-specific increases in the activity of brain areas that process reward and establish cognitive control
Scientific Reports (2018)
-
Association between hedonic hunger and body-mass index versus obesity status
Scientific Reports (2018)
