Volkow ND, Wang GJ, Telang F, Fowler JS, Thanos PK, Logan J et al. Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors. NeuroImage 42: 1537-1543

National Institute on Drug Abuse, Bethesda MD 20892, USA.
NeuroImage (Impact Factor: 6.36). 06/2008; 42(4):1537-43. DOI: 10.1016/j.neuroimage.2008.06.002
Source: PubMed


Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI>40 kg/m(2)) and compared it to that in twelve non-obese controls. PET was used with [(11)C]raclopride to assess D2 receptors and with [(18)F]FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food.

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Available from: Panayotis Thanos, Oct 08, 2015
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    • "As such, differences in reactivity to external food cues may relate to propensities of weight gain, overweight and obesity. Food consumption is mediated by physiological hunger as well as by its rewarding properties (Volkow et al., 2008), indicating that human eating behaviours are driven by the interaction of need (homeostasis ) and want (reward). The incentive value of food, the allocation of attention towards foods when they are presented, and the motivation which drives subsequent efforts to obtain available food rewards are mediated by complex interactions within key brain areas: the amygdala/hippocampus, insular cortex, orbitofrontal cortex, and the striatum (Dagher, 2009). "
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    ABSTRACT: Heightened food cue-reactivity in overweight and obese individuals has been related to aberrant functioning of neural circuitry implicated in motivational behaviours and reward-seeking. Here we explore the neurophysiology of visual food cue-reactivity in overweight and obese women, as compared with normal weight women, by assessing differences in cortical arousal and attentional processing elicited by food and neutral image inserts in a Stroop task with record of EEG spectral band power and ERP responses. Results show excess right frontal (F8) and left central (C3) relative beta band activity in overweight women during food task performance (indicative of pronounced early visual cue-reactivity) and blunted prefrontal (Fp1 and Fp2) theta band activity in obese women during office task performance (suggestive of executive dysfunction). Moreover, as compared to normal weight women, food images elicited greater right parietal (P4) ERP P200 amplitude in overweight women (denoting pronounced early attentional processing) and shorter right parietal (P4) ERP P300 latency in obese women (signifying enhanced and efficient maintained attentional processing). Differential measures of cortical arousal and attentional processing showed significant correlations with self-reported eating behaviour and body shape dissatisfaction, as well as with objectively assessed percent fat mass. The findings of the present study suggest that heightened food cue-reactivity can be neurophysiologically measured, that different neural circuits are implicated in the pathogenesis of overweight and obesity, and that EEG techniques may serve useful in the identification of endophenotypic markers associated with an increased risk of externally mediated food consumption. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Appetite 11/2014; 85. DOI:10.1016/j.appet.2014.11.012 · 2.69 Impact Factor
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    • "In addition, we showed that the dopamine D2 receptor content was decreased in the nucleus accumbens of the SL animals. It is shown in humans that striatal dopamine D2 receptor availability is lower in obese individuals compared to controls [51] [52] [53]. We had previously demonstrated that the SL animals had increased abdominal fat deposition in adulthood [42], which is in agreement with other rodent data showing that abdominal obesity is associated with diminished D2 availability in striatal areas [54] [55]. "
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    ABSTRACT: Postnatal overfeeding is a well-known model of early-life induced obesity and glucose intolerance in rats. However, little is known about its impact on insulin signaling in specific brain regions such as the mesocorticolimbic system, and its putative effects on dopamine-related hedonic food intake in adulthood. For this study, rat litters were standardized to 4 (small litter -SL) or 8 pups (control - NL) at postnatal day 1. Weaning was at day 21, and all tests were conducted after day 60 of life in male rats. In Experiment 1, we demonstrated that the SL animals were heavier than the NL at all time points and had decreased AKT/pAKT ratio in the Ventral Tegmental Area (VTA), without differences in the skeletal muscle insulin signaling in response to insulin injection. In Experiment 2, the standard rat chow intake was addressed using an automated system (BioDAQ, Research Diets®), and showed no differences between the groups. On the other hand, the SL animals ingested more sweet food in response to the 1min. tail-pinch challenge and did not develop conditioned place preference to sweet food. In Experiment 3 we showed that the SL rats had increased VTA TH content but had no difference in this protein in response to a sweet food challenge, as the NL had. The SL rats also showed decreased levels of dopamine D2 receptors in the nucleus accumbens. Here we showed that early postnatal overfeeding was linked to an altered functioning of the mesolimbic dopamine pathway, which was associated with altered insulin signaling in the VTA, suggesting increased sensitivity, and expression of important proteins of the dopaminergic system.
    Behavioural Brain Research 09/2014; DOI:10.1016/j.bbr.2014.09.033 · 3.03 Impact Factor
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    • "Interestingly, DA-system integrity may be influenced by lifestyle factors. For example, cognitive and physical training increase dopaminergic measures , such as extracellular levels and receptor expression (Bäckman et al., 2011; de Castro and Duncan, 1985; Gilliam et al., 1984; MacRae et al., 1987; McNab et al., 2009; Vuckovic et al., 2010), whereas depression and obesity are associated with reductions (Meyer et al., 2001; Wang et al., 2001; Volkow et al., 2008). When it comes to heritage, normal genetic variants induce interindividual variability in brain and cognition (Knickmeyer et al., 2014; Lindenberger et al., 2008; Malhotra et al., 2002; Nyberg et al., 2013). "
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    Brain Research 09/2014; 1612. DOI:10.1016/j.brainres.2014.09.010 · 2.84 Impact Factor
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