Aging Research Center, Karolinska Institute and Stockholm University, S-17177 Stockholm, Sweden.
Department of Radiation Sciences, Umeå University, S-90187 Umeå, Sweden.
Cereb Cortex. 2020 Mar 14;30(3):989-1000. doi: 10.1093/cercor/bhz142.
Insufficient or excessive dopaminergic tone impairs cognitive performance. We examine whether the balance between transmitter availability and dopamine (DA) D2 receptors (D2DRs) is important for successful memory performance in a large sample of adults (n = 175, 64-68 years). The Catechol-O-Methyltransferase polymorphism served as genetic proxy for endogenous prefrontal DA availability, and D2DRs in dorsolateral prefrontal cortex (dlPFC) were measured with [11C]raclopride-PET. Individuals for whom D2DR status matched DA availability showed higher levels of episodic and working-memory performance than individuals with insufficient or excessive DA availability relative to the number of receptors. A similar pattern restricted to episodic memory was observed for D2DRs in caudate. Functional magnetic resonance imaging data acquired during working-memory performance confirmed the importance of a balanced DA system for load-dependent brain activity in dlPFC. Our data suggest that the inverted-U-shaped function relating DA signaling to cognition is modulated by a dynamic association between DA availability and receptor status.
多巴胺能张力不足或过度都会损害认知表现。我们在一个包含大量成年人的样本（n=175，64-68 岁）中检验了递质可用性与多巴胺（DA）D2 受体（D2DR）之间的平衡对于成功的记忆表现是否重要。儿茶酚-O-甲基转移酶多态性可作为前额叶 DA 可用性的遗传替代物，并用 [11C]raclopride-PET 测量背外侧前额叶皮质（dlPFC）中的 D2DR。与受体数量相比，D2DR 状态与 DA 可用性匹配的个体比 DA 可用性不足或过度的个体具有更高的情景和工作记忆表现水平。尾状核中的 D2DR 也观察到了仅限于情景记忆的类似模式。在工作记忆表现期间获得的功能磁共振成像数据证实了平衡的 DA 系统对于 dlPFC 中与负荷相关的大脑活动的重要性。我们的数据表明，与认知相关的 DA 信号的倒 U 形功能受到 DA 可用性和受体状态之间动态关联的调节。
