Morton and Gloria Shulman Movement Disorder Unit & E.J. Safra Parkinson Disease Program, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada.
Neurobiol Dis. 2012 Dec;48(3):519-25. doi: 10.1016/j.nbd.2012.06.021. Epub 2012 Jul 3.
Impulse control disorders such as pathological gambling (PG) are a serious and common adverse effect of dopamine (DA) replacement medication in Parkinson's disease (PD). Patients with PG have increased impulsivity and abnormalities in striatal DA, in common with behavioural and substance addictions in the non-PD population. To date, no studies have investigated the role of extrastriatal dopaminergic abnormalities in PD patients with PG. We used the PET radiotracer, [11C] FLB-457, with high-affinity for extrastriatal DA D2/3 receptors. 14 PD patients on DA agonists were imaged while they performed a gambling task involving real monetary reward and a control task. Trait impulsivity was measured with the Barratt Impulsivity Scale (BIS). Seven of the patients had a history of PG that developed subsequent to DA agonist medication. Change in [11C] FLB-457 binding potential (BP) during gambling was reduced in PD with PG patients in the midbrain, where D2/D3 receptors are dominated by autoreceptors. The degree of change in [11C] FLB-457 binding in this region correlated with impulsivity. In the cortex, [11C] FLB-457 BP was significantly greater in the anterior cingulate cortex (ACC) in PD patients with PG during the control task, and binding in this region was also correlated with impulsivity. Our findings provide the first evidence that PD patients with PG have dysfunctional activation of DA autoreceptors in the midbrain and low DA tone in the ACC. Thus, altered striatal and cortical DA homeostasis may incur vulnerability for the development of PG in PD, linked with the impulsive personality trait.
冲动控制障碍，如病理性赌博（PG），是帕金森病（PD）患者多巴胺（DA）替代药物的一种严重且常见的不良反应。PG 患者的冲动性增加和纹状体 DA 异常与非 PD 人群中的行为和物质成瘾相同。迄今为止，尚无研究调查 PD 伴 PG 患者的纹状体外多巴胺能异常的作用。我们使用具有高亲和力的 [11C] FLB-457 作为 PET 示踪剂，用于检测纹状体外 DA D2/3 受体。14 名正在服用 DA 激动剂的 PD 患者接受了 [11C] FLB-457 正电子发射断层扫描（PET），同时进行了涉及真实货币奖励的赌博任务和对照任务。特质冲动性通过巴雷特冲动量表（BIS）进行测量。其中 7 名患者在 DA 激动剂治疗后出现 PG 病史。在中脑，DA2/3 受体主要由自身受体支配，PG 伴 PD 患者在赌博过程中 [11C] FLB-457 结合潜能（BP）的变化减少。该区域 [11C] FLB-457 结合的变化程度与冲动性相关。在大脑皮层，PG 伴 PD 患者在对照任务期间，ACC 中的 [11C] FLB-457 BP 在前扣带回皮层（ACC）显著升高，该区域的结合也与冲动性相关。我们的发现首次提供了证据，表明 PD 伴 PG 患者的中脑 DA 自身受体功能障碍和 ACC 中的 DA 张力降低。因此，纹状体和皮质 DA 稳态的改变可能会导致 PD 中 PG 的易感性增加，这与冲动性人格特质有关。
