The neurotransmitter dopamine is important in the regulation of food intake. It is hypothesised that obese people experience less reward from food due to lower striatal dopamine release, which consequently leads to overeating. This study is the first to assess whether obese subjects have blunted striatal dopamine release.
Method:
We measured striatal dopamine D2/3 receptor (DRD2/3) availability and amphetamine-induced striatal dopamine release in 15 obese and 15 age-matched, normal-weight women using [123I]iodobenzamide single photon emission computed tomography (SPECT) imaging. In addition, correlations with food craving were examined.
Results:
Baseline striatal DRD2/3 availability was lower in obese subjects (0.91±0.16) compared to controls (1.09±0.16; p=0.006). Amphetamine-induced dopamine release was significant in controls (7.5%±9.2; p=0.007) and not in obese subjects (1.2%±17.7; p=0.802), although the difference in release between groups (d=0.45) was not significant. Dopamine release positively correlated with the trait food craving in obese subjects.
Conclusion:
This study replicates previous findings of lower striatal DRD2/3 availability in obesity and provides preliminary data that obesity is associated with blunted dopamine release. The positive correlation between dopamine release and food craving in obesity may seem contradictory with the latter finding but is presumably related to heterogeneity within the obese subjects.
AvenaNMRadaPHoebelBG (2008) Evidence for sugar addiction: Behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev32: 20–39.
2.
BooijJKornPLinszenDH. (1997) Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography. Eur J Nucl Med24: 674–677.
3.
BootEBooijJHaslerG. (2008) AMPT-induced monoamine depletion in humans: Evaluation of two alternative [123I]IBZM SPECT procedures. Eur J Nucl Med Mol Imaging35: 1350–1356.
4.
BootEBooijJZinkstokJR. (2010) Striatal D2 receptor binding in 22q11 deletion syndrome: An [123I]IBZM SPECT study. J Psychopharmacol24: 1525–1531.
5.
BuckholtzJWTreadwayMTCowanRL. (2010) Dopaminergic network differences in human impulsivity. Science329: 532.
6.
DavisJFChoiDLSchurdakJD. (2011) Leptin regulates energy balance and motivation through action at distinct neural circuits. Biol Psychiatry69: 668–674.
7.
De WeijerBAvan de GiessenEvan AmelsvoortTA. (2011) Lower striatal dopamine D2/3 receptor availability in obese compared with non-obese subjects. EJNMMI Res1: 37.
8.
DunnJPKesslerRMFeurerID. (2012) Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity. Diabetes Care35: 1105–1111.
9.
GeigerBMHaburcakMAvenaNM. (2009) Deficits of mesolimbic dopamine neurotransmission in rat dietary obesity. Neuroscience159: 1193–1199.
10.
HaltiaLTRinneJOMerisaariH. (2007) Effects of intravenous glucose on dopaminergic function in the human brain in vivo. Synapse61: 748–756.
11.
JerlhagEEgeciogluEDicksonSL. (2011) Glutamatergic regulation of ghrelin-induced activation of the mesolimbic dopamine system. Addict Biol16: 82–91.
12.
JohnsonPMKennyPJ (2010) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci13: 635–641.
13.
KegelesLSZea-PonceYAbi-DarghamA. (1999) Stability of [123I]IBZM SPECT measurement of amphetamine-induced striatal dopamine release in humans. Synapse31: 302–308.
14.
KoobGFLeMM (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology24: 97–129.
15.
MartinezDGilRSlifsteinM. (2005) Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum. Biol Psychiatry58: 779–786.
16.
MartinezDNarendranRFoltinRW. (2007) Amphetamine-induced dopamine release: Markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am J Psychiatry164: 622–629.
17.
MartinezDSacconePALiuF. (2012) Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: Commonalities and differences with other types of addiction. Biol Psychiatry71: 192–198.
18.
MichaelidesMThanosPKKimR. (2012) PET imaging predicts future body weight and cocaine preference. Neuroimage59: 1508–1513.
MunroCAMcCaulMEWongDF. (2006) Sex differences in striatal dopamine release in healthy adults. Biol Psychiatry59: 966–974.
21.
NarayanaswamiVThompsonACCassisLA. (2013) Diet-induced obesity: Dopamine transporter function, impulsivity and motivation. Int J Obes (Lond)37: 1095–1103.
22.
NarendranRMartinezD (2008) Cocaine abuse and sensitization of striatal dopamine transmission: A critical review of the preclinical and clinical imaging literature. Synapse62: 851–869.
23.
NijsIMFrankenIHMurisP (2007) The modified Trait and State Food-Cravings Questionnaires: Development and validation of a general index of food craving. Appetite49: 38–46.
24.
PaiMPPaloucekFP (2000) The origin of the ‘ideal’ body weight equations. Ann Pharmacother34: 1066–1069.
25.
RinneJOHietalaJRuotsalainenU. (1993) Decrease in human striatal dopamine D2 receptor density with age: A PET study with [11C]raclopride. J Cereb Blood Flow Metab13: 310–314.
26.
RothemundYPreuschhofCBohnerG. (2007) Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals. Neuroimage37: 410–421.
27.
SchifferWKVolkowNDFowlerJS. (2006) Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine. Synapse59: 243–251.
28.
SmallDMJones-GotmanMDagherA (2003) Feeding-induced dopamine release in dorsal striatum correlates with meal pleasantness ratings in healthy human volunteers. Neuroimage19: 1709–1715.
29.
SticeESpoorSBohonC. (2008) Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science322: 449–452.
30.
SticeESpoorSNgJ. (2009) Relation of obesity to consummatory and anticipatory food reward. Physiol Behav97: 551–560.
31.
StoeckelLEWellerRECookEWIII. (2008) Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage41: 636–647.
32.
Van de GiessenELa FleurSEde BruinCM. (2012) Free-choice and no-choice high fat diets affect striatal dopamine D(2/3) receptor availability, caloric intake, and adiposity. Obesity (Silver Spring) 20: 1738–1740.
33.
Van KammenDPMurphyDL (1975) Attenuation of the euphoriant and activating effects of d- and l-amphetamine by lithium carbonate treatment. Psychopharmacologia44: 215–224.
34.
VolkowNDWiseRA (2005) How can drug addiction help us understand obesity?Nat Neurosci8: 555–560.
35.
VolkowNDWangGJBalerRD (2011) Reward, dopamine and the control of food intake: Implications for obesity. Trends Cogn Sci15: 37–46.
VolkowNDWangGJTelangF. (2007) Profound decreases in dopamine release in striatum in detoxified alcoholics: Possible orbitofrontal involvement. J Neurosci27: 12700–12706.
38.
WangGJGeliebterAVolkowND. (2011) Enhanced striatal dopamine release during food stimulation in binge eating disorder. Obesity (Silver Spring) 19: 1601–1608.
39.
WangGJVolkowNDLoganJ. (2001) Brain dopamine and obesity. Lancet357: 354–357.
40.
WilcoxCEBraskieMNKluthJT. (2010) Overeating behavior and striatal dopamine with 6-[F]-Fluoro-L-m-Tyrosine PET. J Obes2010: Article ID 909348.
41.
ZiauddeenHFarooqiISFletcherPC (2012) Obesity and the brain: How convincing is the addiction model?Nat Rev Neurosci13: 279–286.
