Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Sleep Med. 2011 Jan;12(1):41-6. doi: 10.1016/j.sleep.2010.07.009. Epub 2010 Nov 1.
To evaluate the clinical and biological effects of chronic pramipexole (PPX) therapy in a proposed animal model of restless legs syndrome (RLS).
We developed an animal model of RLS with iron deprivation (ID) plus bilateral 6-hydroxydopamine (6-OHDA) lesions in the A11 nuclei in C57BL/6 mice, which showed increased locomotor activities that lessened by application of the dopamine agonist PPX. The mice were treated with PPX for a period of 28 (short-term observation) and 84 days (long-term observation). We measured the behavioral performances, iron levels, monoamine contents, and dopamine receptor bindings in the spinal cord after treatment.
C57BL/6 mice with ID diet plus 6-OHDA lesions in A11 nuclei showed significantly increased movement (Moving Time increased by 186% and total travel distance increased by 162%). Acute and chronic treatment with three doses of PPX (0.1 mg/kg, 0.5 mg/kg, and 2.5 mg/kg) attenuated locomotor activities in the mice. Biochemical assays demonstrated that the ID+6-OHDA mice had significant lower levels of dopamine and HVA, and D2 receptor density in the lumbar cord. Chronic treatment with PPX did not significantly alter dopamine or serotonin metabolites in the lumbar cord. There was a trend to mildly decreased D3, but not D1 or D2 receptor density. PPX treatment also caused a modestly increased D1, but not D2 or D3, receptor affinity. The reduction in spinal cord iron seen in the ID+6-OHDA mice was partially attenuated by long-term PPX treatment compared to untreated animals.
Pramipexole produced long-term improvement of the RLS-like symptoms in our proposed animal model, caused a partial recovery of spinal iron deficiency, and modestly increased D1 receptor affinity.
评估慢性普拉克索（PPX）治疗拟用于治疗不宁腿综合征（RLS）的动物模型的临床和生物学效应。
我们通过铁剥夺（ID）和双侧 A11 核内 6-羟多巴胺（6-OHDA）损伤建立了 RLS 动物模型，该模型表现为运动活动增加，应用多巴胺激动剂 PPX 后减轻。用 PPX 对小鼠进行 28 天（短期观察）和 84 天（长期观察）的治疗。治疗后测量行为表现、铁水平、单胺含量和脊髓多巴胺受体结合。
ID 饮食加 A11 核内 6-OHDA 损伤的 C57BL/6 小鼠运动显著增加（运动时间增加 186%，总行程增加 162%）。三种剂量的 PPX（0.1 mg/kg、0.5 mg/kg 和 2.5 mg/kg）的急性和慢性治疗均可减轻小鼠的运动活动。生化分析表明，ID+6-OHDA 小鼠的脊髓多巴胺和 HVA 以及 D2 受体密度显著降低。慢性 PPX 治疗对脊髓多巴胺代谢物和 5-羟色胺代谢物无显著影响。D3 受体密度略有降低，但 D1 或 D2 受体密度无变化。PPX 治疗还导致 D1 受体亲和力适度增加，但 D2 或 D3 受体亲和力无变化。与未治疗动物相比，长期 PPX 治疗部分减轻了 ID+6-OHDA 小鼠脊髓铁减少。
在我们提出的动物模型中，普拉克索治疗可长期改善 RLS 样症状，部分恢复脊髓铁缺乏，并适度增加 D1 受体亲和力。
