Age-related changes in midbrain dopaminergic regulation of the human reward system
Age-related changes in midbrain dopaminergic regulation of the human reward system
复制标题
DOI：
10.1073/pnas.0802127105
复制
发表时间：
2008-09-30
影响因子：
11.1
通讯作者：
Berman, Karen Faith
中科院分区：
文献类型：
--
作者：
Dreher, Jean-Claude;Meyer-Lindenberg, Andreas;Berman, Karen Faith
多巴胺系统在奖赏过程中起着至关重要的作用，特别容易受到衰老的影响。据报道，多巴胺受体和转运蛋白在正常寿命期间会发生显著损失，但对这种与年龄相关的多巴胺能下降的神经功能后果知之甚少。在动物身上，大量的数据表明，中脑的多巴胺活动与奖励过程密切相关。在人类中，虽然药理学和临床研究的间接证据也支持这种关联，但没有直接证明中脑多巴胺和奖励相关神经反应之间的联系。此外，在老年人中没有这种关系改变的体内数据。在这里，通过使用6-[（18）F]氟多巴（FDOPA）正电子发射断层扫描（PET）和事件相关的3 T功能磁共振成像（fMRI）在同一受试者中，我们直接证明了人类中脑多巴胺合成和奖励相关的前额叶活动之间的联系，表明健康的衰老诱导奖励系统的功能改变，并确定中脑多巴胺合成和前额叶活动之间的关系方向（从正相关到负相关）的年龄相关变化。这些结果表明，年龄依赖性的多巴胺能调谐机制皮层奖励处理，并提供系统级的信息，在健康老龄化的关键神经回路的改变。总之，我们的研究结果提供了健康年轻人和老年受试者中脑多巴胺功能和奖励系统之间相互作用的重要特征，并确定了伴随衰老的调节回路的变化。
The dopamine system, which plays a crucial role in reward processing, is particularly vulnerable to aging. Significant losses over a normal lifespan have been reported for dopamine receptors and transporters, but very little is known about the neurofunctional consequences of this age-related dopaminergic decline. In animals, a substantial body of data indicates that dopamine activity in the midbrain is tightly associated with reward processing. In humans, although indirect evidence from pharmacological and clinical studies also supports such an association, there has been no direct demonstration of a link between midbrain dopamine and reward-related neural response. Moreover, there are no in vivo data for alterations in this relationship in older humans. Here, by using 6-[(18)F] FluoroDOPA (FDOPA) positron emission tomography (PET) and event-related 3T functional magnetic resonance imaging (fMRI) in the same subjects, we directly demonstrate a link between midbrain dopamine synthesis and reward-related prefrontal activity in humans, show that healthy aging induces functional alterations in the reward system, and identify an age-related change in the direction of the relationship (from a positive to a negative correlation) between midbrain dopamine synthesis and prefrontal activity. These results indicate an age-dependent dopaminergic tuning mechanism for cortical reward processing and provide system-level information about alteration of a key neural circuit in healthy aging. Taken together, our findings provide an important characterization of the interactions between midbrain dopamine function and the reward system in healthy young humans and older subjects, and identify the changes in this regulatory circuit that accompany aging.