Neurodegenerative Disease Group, Montreal Neurological Institute-Hospital (The Neuro), 3801 University St, Montreal, QC, H3A 2B4, Canada.
Comparative Medicine & Animal Resource Centre, McGill University, Montreal, QC, Canada.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Aug;394(8):1685-1692. doi: 10.1007/s00210-021-02090-6. Epub 2021 May 8.
Parkinson's disease (PD) psychosis afflicts over half of patients and poses a significant burden on quality of life. The aetiology of PD psychosis is multifactorial and likely arises from the complex interaction between dopamine replacement therapy and disease state. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned common marmoset is a validated model to predict the efficacy of therapeutic compounds for treatment-related complications, including PD psychosis. In this model, psychosis-like behaviours (PLBs) encompass stereotypies that are idiosyncratic in nature and reproducible with each L-3,4-dihydroxyphenylanaline (L-DOPA) administration. In the present study, we sought to expand upon the existing repertoire of PLBs through the characterisation of novel stereotypical behaviours that appear dependent on the environment. We then discuss our findings in the context of clinical reports on stereotypical behaviours termed "punding" in subjects with PD, which consists of stereotypical repetitive and senseless behaviours. The poor understanding of the pathophysiology governing punding and consequent lack of effective therapies stand to benefit from enhanced characterisation of these stereotypical behaviours in a validated pre-clinical model. We hope that further characterisation of PLBs in the MPTP-lesioned marmoset will be helpful in the evaluation of interventions that seek to alleviate PD psychosis symptoms.
帕金森病（PD）精神病影响超过一半的患者，并对生活质量造成重大负担。PD 精神病的病因是多因素的，可能是由于多巴胺替代疗法和疾病状态之间的复杂相互作用引起的。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）损伤的普通狨猴是一种经过验证的模型，可以预测治疗相关化合物治疗相关并发症的疗效，包括 PD 精神病。在该模型中，类精神病行为（PLB）包括刻板行为，这些行为具有独特的性质，可以通过每次 L-3,4-二羟基苯丙氨酸（L-DOPA）给药来重现。在本研究中，我们试图通过描述新的刻板行为来扩展现有的 PLB 谱，这些行为似乎依赖于环境。然后，我们根据临床报告中关于刻板行为的发现进行讨论，这些行为在 PD 患者中被称为“冲动行为”，包括刻板的重复和无意义的行为。由于对管理冲动行为的病理生理学的理解不足，以及缺乏有效的治疗方法，因此需要从经过验证的临床前模型中对这些刻板行为进行更深入的描述，以从中受益。我们希望进一步描述 MPTP 损伤的狨猴中的 PLB 将有助于评估旨在缓解 PD 精神病症状的干预措施。
