Division of Brain, Imaging and Behaviour–Systems Neuroscience, BIB-SN, Toronto Western Research Institute, University of Toronto, Canada.
Neurology. 2010 Nov 9;75(19):1711-6. doi: 10.1212/WNL.0b013e3181fc27fa. Epub 2010 Oct 6.
Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).
Following overnight withdrawal of antiparkinsonian medication, patients were studied with H₂(15)O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.
We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.
We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions--outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)--together with restricted access of those areas to executive control (external pallidum)--may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.
一些帕金森病（PD）患者在接受多巴胺激动剂（DAs）治疗时会出现病理性赌博。然而，对于可能导致易患个体行为改变的多巴胺诱导的神经元网络变化知之甚少。在这项病例对照研究中，我们旨在研究多巴胺诱导的大脑活动变化，这些变化可能有助于将有 DA 诱导病理性赌博（赌徒）病史的 PD 患者与无此类病史的 PD 患者（对照组）区分开来。
在停止使用抗帕金森病药物过夜后，患者在给予 DA（3mg 阿朴吗啡）前后接受 H₂（15）O PET 检查，以测量在概率反馈的卡片选择游戏中，区域脑血流变化作为区域大脑活动的指标。
我们观察到，在与冲动控制和反应抑制相关的大脑区域中，与 DA 相关的活动变化方向将赌徒与对照组区分开来。在对照组中，DA 显著增加了这些区域的活动，而赌徒则表现出明显的 DA 诱导的活动减少。
我们提出，在易患 PD 的患者中，DAs 产生了一种异常的神经元模式，类似于非帕金森氏病理性赌博和药物成瘾中发现的模式。DA 诱导的抑制关键功能（扣带前回、杏仁核和外侧眶额皮层）的破坏，以及这些区域对执行控制（苍白球外）的限制，可能很好地解释了易患 PD 患者的冲动控制和反应抑制丧失，从而促进了病理性赌博的发展。
