Biodonostia Research Institute, 20014 San Sebastián, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.
University Hospital Donostia, 20014 San Sebastián, Spain.
Neurosci Biobehav Rev. 2015 Sep;56:294-314. doi: 10.1016/j.neubiorev.2015.07.010. Epub 2015 Jul 26.
Dopaminergic treatment in Parkinson's disease (PD) reduces the severity of motor symptoms of the disease. However, its chronic use is associated with disabling motor and behavioral side effects, among which levodopa-induced dyskinesias (LID) and impulse control disorders (ICD) are the most common. The underlying mechanisms and pathological substrate of these dopaminergic complications are not fully understood. Recently, the refinement of imaging techniques and the study of the genetics and molecular bases of LID and ICD indicate that, although different, they could share some features. In addition, animal models of parkinsonism with LID have provided important knowledge about mechanisms underlying such complications. In contrast, animal models of parkinsonism and abnormal impulsivity, although useful regarding some aspects of human ICD, do not fully resemble the clinical phenotype of ICD in patients with PD, and until now have provided limited information. Studies on animal models of addiction could complement the previous models and provide some insights into the background of these behavioral complications given that ICD are regarded as behavioral addictions. Here we review the most relevant advances in relation to imaging, genetics, biochemistry and pharmacological interventions to treat LID and ICD in patients with PD and in animal models with a view to better understand the overlapping and unique maladaptations to dopaminergic therapy that are associated with LID and ICD.
在帕金森病（PD）中，多巴胺能治疗可减轻疾病的运动症状严重程度。然而，其长期使用与致残的运动和行为副作用相关，其中左旋多巴诱导的运动障碍（LID）和冲动控制障碍（ICD）最为常见。这些多巴胺能并发症的潜在机制和病理基础尚未完全阐明。最近，成像技术的精细化以及对 LID 和 ICD 的遗传学和分子基础的研究表明，尽管它们不同，但它们可能具有一些共同特征。此外，具有 LID 的帕金森病动物模型为这些并发症的潜在机制提供了重要知识。相比之下，帕金森病和异常冲动性的动物模型，尽管在某些方面对人类 ICD 有用，但并不完全类似于 PD 患者 ICD 的临床表型，且迄今为止提供的信息有限。成瘾动物模型的研究可以补充上述模型，并为这些行为并发症的背景提供一些见解，因为 ICD 被视为行为成瘾。本文综述了与 PD 患者的 LID 和 ICD 以及具有 LID 的动物模型的影像学、遗传学、生物化学和药理学干预相关的最相关进展，以期更好地理解与 LID 和 ICD 相关的多巴胺能治疗的重叠和独特适应不良。
