title: Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors.
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/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.
authors.affiliation: National Institute on Drug Abuse, Bethesda MD 20892, USA. nvolkow@nida.nih.gov
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Gene-Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Frank
authors.initials: F
authors.lastname: Telang
authors.forename: Joanna S
authors.initials: JS
authors.lastname: Fowler
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
authors.forename: Jean
authors.initials: J
authors.lastname: Logan
authors.forename: David
authors.initials: D
authors.lastname: Alexoff
authors.forename: Yu-Shin
authors.initials: YS
authors.lastname: Ding
authors.forename: Christopher
authors.initials: C
authors.lastname: Wong
authors.forename: Yeming
authors.initials: Y
authors.lastname: Ma
authors.forename: Kith
authors.initials: K
authors.lastname: Pradhan
mesh_terms: D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D017448:Receptors, Dopamine D2