Caravaggio Fernando, Raitsin Sofia, Gerretsen Philip, Nakajima Shinichiro, Wilson Alan, Graff-Guerrero Ariel
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Biol Psychiatry. 2015 Jan 15;77(2):196-202. doi: 10.1016/j.biopsych.2013.02.017. Epub 2013 Mar 27.
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 [(11)C]-(+)-PHNO (n = 26) and the antagonist [(11)C]-raclopride (n = 35) in healthy humans.
In the VS, we found a positive correlation between BMI and [(11)C]-(+)-PHNO binding but no relationship with [(11)C]-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.
正电子发射断层扫描研究表明，在肥胖个体中，多巴胺D2/3受体（D2/3R）的可利用性与体重指数（BMI）呈负相关，但在健康个体中并非如此。然而，以往的正电子发射断层扫描研究并未专门观察腹侧纹状体（VS），而腹侧纹状体在动机和进食中起重要作用。此外，这些研究仅使用了拮抗剂放射性示踪剂。自由获取高脂饮食的正常体重大鼠对D2/3R激动剂表现出行为敏化，但对拮抗剂无此反应。敏化与D2/3R亲和力增加有关，这会影响激动剂的结合，但不影响拮抗剂的结合。
我们在健康人类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），研究了非肥胖范围内（18.6 - 27.8）的BMI与VS中D2/3R可利用性之间的关联。
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，两种放射性示踪剂在背侧纹状体中，BMI与结合均无相关性。
我们提出，在非肥胖个体中，较高的BMI可能与VS中D2R亲和力增加有关。这种增加的亲和力可能会增强食物线索的激励显著性，并抵消饱腹感线索的作用，从而增加进食。
