Elsevier

NeuroImage

Volume 42, Issue 4, 1 October 2008, Pages 1537-1543
NeuroImage

Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: Possible contributing factors

https://doi.org/10.1016/j.neuroimage.2008.06.002Get rights and content

Abstract

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/m2) and compared it to that in twelve non-obese controls. PET was used with [11C]raclopride to assess D2 receptors and with [18F]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.

Section snippets

Subjects

Ten morbidly obese subjects (5 women and 5 men, mean 35.9 ± 10 years of age) with mean body mass (BMI: weight in kilograms divided by the square of height in meters) of 51 ± 5 kg/m2 were selected from a pool of obese subjects who responded to an advertisement. Twelve non-obese subjects (6 women and 6 men, mean 33.2 ± 8 years of age) with mean BMI of 25 ± 3 kg/m2 were selected for comparison. Participants were screened carefully with a detailed medical history, physical and neurological examination,

Results

The measures of striatal D2 receptor availability (Bmax/Kd) were significantly lower in the obese subjects than in the non-obese controls (2.72 ± 0.5 versus 3.14 ± 0.40, Student t test = 2.2, P < 0.05).

The SPM analysis done on the obese subjects to assess the correlation between D2 receptor availability and regional brain glucose metabolism showed it was significant in 4 clusters that were centered in (1) left and right prefrontal (BA 9), CG (BA 32) and left lateral orbitofrontal cortices (BA 45): (2)

Discussion

Here we show that in morbidly obese subjects DA D2 receptor availability was associated with metabolic activity in prefrontal regions (DLPFC, medial orbitofrontal cortex and anterior CG). These regions have all been implicated in regulating food consumption and in the hyperphagia of obese individuals (Tataranni et al., 1999, Tataranni and DelParigi, 2003). We also show a significant correlation with metabolism in somatosensory cortex (postcentral cortices) that was significant both in obese and

Acknowledgments

We thank David Schlyer, David Alexoff, Paul Vaska, Colleen Shea, Youwen Xu, Pauline Carter, Karen Apelskog, and Linda Thomas for their contributions. This research was supported by NIH's Intramural Research Program (NIAAA) and by DOE (DE-AC01-76CH00016).

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