Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, 63110.
Synapse. 2013 Nov;67(11):748-56. doi: 10.1002/syn.21680. Epub 2013 May 30.
Previous PET imaging studies have demonstrated mixed findings regarding dopamine D2/D3 receptor availability in obese relative to nonobese humans. Nonspecific D2/D3 radioligands do not allow for separate estimation of D2 receptor (D2R) and D3 receptor (D3R) subtypes of the D2 receptor family, which may play different roles in behavior and are distributed differently throughout the brain. These radioligands are also displaceable by endogenous dopamine, confounding interpretation of differences in receptor availability with differing levels of dopamine release. The present study used PET imaging with the D2R-selective radioligand (N-[(11)C] methyl)benperidol ([(11)C]NMB), which is nondisplaceable by endogenous dopamine, to estimate D2R specific binding (BPND) and its relationship to body mass index (BMI) and age in 15 normal-weight (mean BMI = 22.6 kg/m(2)) and 15 obese (mean BMI = 40.3 kg/m(2)) men and women. Subjects with illnesses or taking medications that interfere with dopamine signaling were excluded. Striatal D2R BPND was calculated using the Logan graphical method with cerebellum as a reference region. D2R BPND estimates were higher in putamen and caudate relative to nucleus accumbens, but did not differ between normal-weight and obese groups. BMI values did not correlate with D2R BPND . Age was negatively correlated with putamen D2R BPND in both groups. These results suggest that altered D2R specific binding is not involved in the pathogenesis of obesity per se and underscore the need for additional studies evaluating the relationship between D3R, dopamine reuptake, or endogenous dopamine release and human obesity.
先前的正电子发射断层扫描(PET)成像研究表明,肥胖人群和非肥胖人群相比,其多巴胺 D2/D3 受体的可用性存在差异。非特异性 D2/D3 放射性配体无法单独估计 D2 受体(D2R)和 D3 受体(D3R)这两种 D2 受体家族的亚型,而这两种受体亚型可能在行为方面发挥不同的作用,并且在大脑中的分布也不同。这些放射性配体也可以被内源性多巴胺置换,这使得对受体可用性差异的解释与多巴胺释放水平的差异相混淆。本研究使用 D2R 选择性放射性配体(N-[(11)C]甲基)苯丙醇([(11)C]NMB)进行 PET 成像,该放射性配体不能被内源性多巴胺置换,以估计 15 名正常体重(平均 BMI = 22.6kg/m(2))和 15 名肥胖(平均 BMI = 40.3kg/m(2))的男性和女性的 D2R 特异性结合(BPND)及其与体重指数(BMI)和年龄的关系。患有影响多巴胺信号传递的疾病或正在服用药物的患者被排除在外。纹状体 D2R BPND 使用小脑作为参考区域的 Logan 图形法进行计算。与伏隔核相比,壳核和尾状核的 D2R BPND 估计值更高,但正常体重组和肥胖组之间没有差异。BMI 值与 D2R BPND 不相关。两组的年龄与壳核 D2R BPND 呈负相关。这些结果表明,改变的 D2R 特异性结合本身与肥胖的发病机制无关,这突显了需要进行更多的研究来评估 D3R、多巴胺再摄取或内源性多巴胺释放与人类肥胖之间的关系。