Theis Hendrik, Probst Catharina, Fernagut Pierre-Olivier, van Eimeren Thilo
University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Nuclear Medicine and Department of Neurology, Cologne, Germany.
Université de Poitiers, INSERM, Laboratoire de Neurosciences Expérimentales et Cliniques, Poitiers, France.
NPJ Parkinsons Dis. 2021 Dec 8;7(1):112. doi: 10.1038/s41531-021-00253-z.
Impulse-control disorders are commonly observed during dopamine-replacement therapy in Parkinson's disease, but the majority of patients seems "immune" to this side effect. Epidemiological evidence suggests that a major risk factor may be a specific difference in the layout of the dopaminergic-reinforcement system, of which the ventral striatum is a central player. A series of imaging studies of the dopaminergic system point toward a presynaptic reduction of dopamine-reuptake transporter density and dopamine synthesis capacity. Here, we review current evidence for a vulnerability-stress model in which a relative reduction of dopaminergic projections to the ventral striatum and concomitant sensitization of postsynaptic neurons represent a predisposing (hypodopaminergic) vulnerability. Stress (hyperdopaminergic) is delivered when dopamine replacement therapy leads to a relative overdosing of the already-sensitized ventral striatum. These alterations are consistent with consecutive changes in reinforcement mechanisms, which stimulate learning from reward and impede learning from punishment, thereby fostering the development of impulse-control disorders. This vulnerability-stress model might also provide important insights into the development of addictions in the non-Parkinsonian population.
冲动控制障碍在帕金森病的多巴胺替代治疗期间较为常见，但大多数患者似乎对这种副作用“免疫”。流行病学证据表明，一个主要风险因素可能是多巴胺能强化系统布局的特定差异，其中腹侧纹状体是关键部分。一系列关于多巴胺能系统的影像学研究表明，多巴胺再摄取转运体密度和多巴胺合成能力存在突触前降低。在此，我们综述了当前关于易感性-应激模型的证据，其中多巴胺能投射至腹侧纹状体的相对减少以及突触后神经元的伴随敏化代表了一种易患性（多巴胺能低下）易感性。当多巴胺替代治疗导致已经敏化的腹侧纹状体相对过量时，就会产生应激（多巴胺能亢进）。这些改变与强化机制的连续变化一致，强化机制刺激从奖励中学习并阻碍从惩罚中学习，从而促进冲动控制障碍的发展。这种易感性-应激模型也可能为非帕金森病患者群体成瘾的发展提供重要见解。
