Addictions Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Mov Disord. 2015 Feb;30(2):160-6. doi: 10.1002/mds.26135. Epub 2015 Jan 14.
Dopamine agonist medications with high affinity for the D3 dopamine receptor are commonly used to treat Parkinson's disease, and have been associated with pathological behaviors categorized under the umbrella of impulse control disorders (ICD). The aim of this study was to investigate whether ICD in Parkinson's patients are associated with greater D3 dopamine receptor availability. We used positron emission tomography (PET) radioligand imaging with the D3 dopamine receptor preferring agonist [¹¹C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) in Parkinson's patients with (n = 11) and without (n = 21) ICD, and age-, sex-, and education-matched healthy control subjects (n = 18). Contrary to hypotheses, [¹¹C]-(+)-PHNO binding in D3 -rich brain areas was not elevated in Parkinson's patients with ICD compared with those without; instead, [¹¹C]-(+)-PHNO binding in ventral striatum was 20% lower (P = 0.011), correlating with two measures of ICD severity (r = -0.8 and -0.9), which may reflect higher dopamine tone in ventral striatum. In dorsal striatum, where [¹¹C]-(+)-PHNO binding is associated with D2 receptor levels, [¹¹C]-(+)-PHNO binding was elevated across patients compared with controls. We conclude that although D3 dopamine receptors have been linked to the occurrence of ICD in Parkinson's patients. Our findings do not support the hypothesis that D3 receptor levels are elevated in Parkinson's patients with ICD. We also did not find ICD-related abnormalities in D2 receptor levels. Our findings argue against the possibility that differences in D2/3 receptor levels can account for the development of ICD in PD; however, we cannot rule out that differences in dopamine levels (particularly in ventral striatum) may be involved.
多巴胺激动剂药物对 D3 多巴胺受体具有高亲和力,常用于治疗帕金森病,并与冲动控制障碍 (ICD) 分类下的病理性行为有关。本研究旨在探讨帕金森病患者的 ICD 是否与更大的 D3 多巴胺受体可用性相关。我们使用正电子发射断层扫描 (PET) 放射性配体成像,使用 D3 多巴胺受体优先激动剂 [¹¹C]-(+)-丙基-六氢-萘并恶嗪 ([¹¹C]-(+)-PHNO),对患有 (n = 11) 和不患有 (n = 21) ICD 的帕金森病患者以及年龄、性别和教育程度匹配的健康对照者 (n = 18) 进行了研究。与假设相反,与无 ICD 的帕金森病患者相比,ICD 患者的富含 D3 的大脑区域中的 [¹¹C]-(+)-PHNO 结合并未升高;相反,腹侧纹状体中的 [¹¹C]-(+)-PHNO 结合降低了 20%(P = 0.011),与 ICD 严重程度的两个衡量标准呈正相关(r = -0.8 和 -0.9),这可能反映了腹侧纹状体中较高的多巴胺水平。在与 D2 受体水平相关的背侧纹状体中,与对照组相比,所有患者的 [¹¹C]-(+)-PHNO 结合均升高。我们的结论是,尽管 D3 多巴胺受体与帕金森病患者 ICD 的发生有关,但我们的研究结果并不支持 D3 受体水平在 ICD 帕金森病患者中升高的假设。我们也没有发现 D2 受体水平与 ICD 相关的异常。我们的研究结果排除了 D2/3 受体水平差异可能导致 PD 中 ICD 发展的可能性;然而,我们不能排除多巴胺水平(特别是腹侧纹状体)的差异可能涉及其中。