Ventral striatum binding of a dopamine D2/3 receptor agonist but not antagonist predicts normal body mass index.
Ventral striatum binding of a dopamine D2/3 receptor agonist but not antagonist predicts normal body mass index.
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DOI：
10.1016/j.biopsych.2013.02.017
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发表时间：
2015-01-15
影响因子：
10.6
通讯作者：
Graff-Guerrero, Ariel
中科院分区：
文献类型：
--
作者：
Caravaggio, Fernando;Raitsin, Sofia;Gerretsen, Philip;Nakajima, Shinichiro;Wilson, Alan;Graff-Guerrero, Ariel
正电子发射断层扫描研究表明，多巴胺D2/3受体（D2/3R）的可用性与肥胖者的体重指数（BMI）呈负相关，但在健康受试者中则不然。然而，以前的正电子发射断层扫描研究并没有特别关注腹侧纹状体（VS），这在动机和进食中起着重要作用。此外，这些研究仅使用了拮抗剂放射性示踪剂。正常体重的大鼠给予自由进入高脂饮食表现出行为敏感的D2/3R激动剂，但不是拮抗剂。致敏作用与D2/3R亲和力增加有关，这影响激动剂而不是拮抗剂的结合。我们在健康人中使用激动剂放射性示踪剂[11 C]-（+）-PHNO（n = 26）和拮抗剂[11 C]-雷氯必利（n = 35）检查了非肥胖范围内的BMI（18.6-27.8）与VS中D2/3R可用性之间的关联。在VS中，我们发现BMI与[11 C]-（+）-PHNO结合呈正相关，但与[11 C]-雷氯必利结合无相关性。二次分析显示BMI和背侧纹状体中放射性示踪剂的结合之间没有关系。我们建议，在非肥胖的个人，更高的BMI可能与增加D2 R亲和力的VS。这种增加的亲和力可能会加强食物线索的激励显着性和抵消饱腹感的影响，从而增加喂养。
Positron emission tomography research has shown that dopamine D2/3 receptor (D2/3R) availability is negatively correlated with body mass index (BMI) in obese but not in healthy subjects. However, previous positron emission tomography studies have not looked specifically at the ventral striatum (VS), which plays an important role in motivation and feeding. Furthermore, these studies have only used antagonist radiotracers. Normal-weight rats given free access to high-fat diets demonstrate behavioral sensitization to D2/3R agonists but not to antagonists. Sensitization is associated with increased D2/3R affinity, which affects binding of agonists but not antagonists. We examined the association between BMI within the nonobese range (18.6–27.8) and D2/3R availability in the VS with the use of the agonist radiotracer [11C]-(+)-PHNO (n = 26) and the antagonist [11C]-raclopride (n = 35) in healthy humans. In the VS, we found a positive correlation between BMI and [11C]-(+)-PHNO binding but no relationship with [11C]-raclopride binding. Secondary analyses revealed no relationship between BMI and binding in the dorsal striatum with either radiotracer. We propose that in nonobese individuals, higher BMI may be associated with increased D2R affinity in the VS. This increased affinity may potentiate the incentive salience of food cues and counteract the effects of satiety cues, thereby increasing feeding.
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