Evans Andrew H, Pavese Nicola, Lawrence Andrew D, Tai Yen F, Appel Silke, Doder Miroslava, Brooks David J, Lees Andrew J, Piccini Paola
Reta Lila Weston Institute of Neurological Studies and the National Hospital for Neurology and Neurosurgery, London, United Kingdom.
Ann Neurol. 2006 May;59(5):852-8. doi: 10.1002/ana.20822.
A small group of Parkinson's disease (PD) patients compulsively use dopaminergic drugs despite causing harmful social, psychological, and physical effects and fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition criteria for substance dependence (dopamine dysregulation syndrome [DDS]). We aimed to evaluate levodopa-induced dopamine neurotransmission in the striatum of patients with DDS compared with PD control patients.
We used a two-scan positron emission tomography protocol to calculate the percentage change in (11)C-raclopride binding potential from a baseline withdrawal (off drug) state to the binding potential after an oral dose of levodopa. We related the subjective effects of levodopa to the effects on endogenous dopamine release of a pharmacological challenge with levodopa in eight control PD patients and eight patients with DDS.
PD patients with DDS exhibited enhanced levodopa-induced ventral striatal dopamine release compared with levodopa-treated patients with PD not compulsively taking dopaminergic drugs. The sensitized ventral striatal dopamine neurotransmission produced by levodopa in these individuals correlated with self-reported compulsive drug "wanting" but not "liking" and was related to heightened psychomotor activation (punding).
This provides evidence that links sensitization of ventral striatal circuitry in humans to compulsive drug use.
一小部分帕金森病（PD）患者尽管多巴胺能药物会造成有害的社会、心理和身体影响，仍会强迫性使用，且符合《精神疾病诊断与统计手册》第四版中物质依赖的核心标准（多巴胺调节障碍综合征[DDS]）。我们旨在评估与PD对照患者相比，DDS患者纹状体中左旋多巴诱导的多巴胺神经传递情况。
我们采用两次扫描的正电子发射断层扫描方案，计算从基线撤药（停药）状态到口服一剂左旋多巴后（11）C-雷氯必利结合潜力的百分比变化。我们将左旋多巴的主观效应与左旋多巴药理学激发对内源性多巴胺释放的影响在8名对照PD患者和8名DDS患者中进行了关联。
与未强迫服用多巴胺能药物的左旋多巴治疗的PD患者相比，DDS的PD患者表现出增强的左旋多巴诱导的腹侧纹状体多巴胺释放。左旋多巴在这些个体中产生的致敏腹侧纹状体多巴胺神经传递与自我报告的强迫性药物“渴望”而非“喜好”相关，且与精神运动激活增强（刻板行为）有关。
这提供了将人类腹侧纹状体回路致敏与强迫性药物使用联系起来的证据。
