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Genetic Variation in Dopaminergic Reward in Humans

机译:人类多巴胺能奖赏的遗传变异

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Dopamine-based reward circuitry appears to play a role in encoding reward from eating and incentive sensitization, whereby cues associated with food reward acquire motivational value. Data suggest that low levels of dopamine D2 receptors and attenuated responsivity of dopamine-target regions (e.g. the striatum) to food and food cues are associated with elevated weight. There is mixed evidence that genotypes that appear to be associated with reduced signaling of dopamine circuitry, including DRD2, DRD4 and DAT, are correlated with obesity. In addition, there is emerging fMRI evidence that reduced responsivity in brain regions implicated in food reward increase risk for future weight gain among individuals who appear to be at genetic risk for attenuated dopamine signaling by virtue of DRD2 and DRD4 genotypes. However, it is vital for these relations to be replicated in larger, independent prospective studies and to use positron emission tomography to better characterize parameters of dopamine signaling, including dopamine receptor density, basal dopamine levels, and phasic dopamine release. Improved understanding of the role of dopamine-based reward circuitry and genotypes that influence the functioning of this circuitry may inform the design of more effective preventive and treatment interventions for obesity.
机译:基于多巴胺的奖励电路似乎在编码进食和奖励致敏中的奖励中发挥作用,从而与食物奖励相关的线索获得了激励价值。数据表明,低水平的多巴胺D2受体和多巴胺靶区域(例如纹状体)对食物和食物线索的响应性减弱与体重增加有关。有混合的证据表明,与多巴胺回路信号减少相关的基因型,包括DRD2,DRD4和DAT,与肥胖症相关。另外,有新出现的功能磁共振成像证据表明,由于DRD2和DRD4基因型而具有多巴胺信号减弱遗传风险的个体中,与食物奖励有关的大脑区域响应性降低会增加未来体重增加的风险。然而,在更大的独立前瞻性研究中复制这些关系至关重要,并使用正电子发射断层扫描术更好地表征多巴胺信号传导的参数,包括多巴胺受体密度,基础多巴胺水平和多巴胺释放。对基于多巴胺的奖励电路和影响该电路功能的基因型的作用的更好的了解可能会为肥胖症的设计提供更有效的预防和治疗干预措施。

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