Dopaminergic function and intertemporal choice.
Dopaminergic function and intertemporal choice.
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DOI：
10.1038/tp.2014.133
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发表时间：
2015-01-06
影响因子：
6.8
通讯作者：
Kaasinen V
中科院分区：
文献类型：
--
作者：
Joutsa J;Voon V;Johansson J;Niemelä S;Bergman J;Kaasinen V
延迟奖励的折扣，也被称为时间或延迟折扣，是日常决策的内在因素，在成瘾障碍等病理状态下可能会受到损害。临床前和人体研究表明，多巴胺能功能在时间折扣中的作用，但这种关系尚未通过活体人脑的分子成像得到证实。在这里，我们使用正电子发射断层扫描（PET）评估了两种不同的多巴胺能配体在时间折扣中的多巴胺能功能，评估了三个显示时间折扣受损的人群。首先，我们使用[11C]raclopride PET表明，在病理性赌徒中，更大的时间折扣与腹侧纹状体结合电位降低相关，与高冲动啮齿动物中伏隔核D2/D3受体密度较低的翻译结果一致。时间折扣也与低腹侧纹状体多巴胺释放有关，这表明多巴胺介导的大延迟奖励贬值可能驱动选择偏好。其次，我们使用[18F]氟多巴PET显示，在帕金森病中，颞叶折扣与更大的左尾状多巴胺能终端功能相关。最后，在帕金森病和多巴胺药物诱导的行为成瘾的受试者中，时间折扣与前壳核中更大的多巴胺能终端功能进一步相关。这些发现为纹状体多巴胺功能与时间折扣之间的关系及其在病理疾病中的潜在作用和治疗干预机制提供了见解。
The discounting of delayed rewards, also known as temporal or delay discounting, is intrinsic to everyday decisions and can be impaired in pathological states such as addiction disorders. Preclinical and human studies suggest a role for dopaminergic function in temporal discounting but this relationship has not yet been verified using molecular imaging of the living human brain. Here, we evaluated dopaminergic function in temporal discounting using positron emission tomography (PET) with two different dopaminergic ligands assessing three populations in whom temporal discounting has been shown to be impaired. First, we show using [11C]raclopride PET that in pathological gamblers, greater temporal discounting correlates with decreased ventral striatal binding potential, convergent with translational findings of lower nucleus accumbens D2/D3 receptor density in high-impulsive rodents. Temporal discounting also correlates with lower ventral striatal dopamine release in response to high-reward magnitude suggesting that dopamine-mediated devaluation of larger delayed rewards may drive choice preferences. Second, we show using [18F]fluorodopa PET that in Parkinson's disease, temporal discounting correlates with greater left caudate dopaminergic terminal function. Finally, in subjects with Parkinson's disease and dopamine medication-induced behavioral addictions, temporal discounting is further correlated with greater dopaminergic terminal function in the anterior putamen. These findings provide insights into the relationship between striatal dopamine function and temporal discounting, and its potential role in pathological disorders and mechanisms underlying treatment interventions.
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