RATIONALE Impulse control disorders (ICD) and other impulsive-compulsive behaviours are frequently found in Parkinson's disease (PD) patients treated with dopaminergic agonists. To date, there are no available animal models to investigate their pathophysiology and determine whether they can be elicited by varying doses of dopaminergic drugs. In addition, there is some controversy regarding the predispositional pattern of striatal dopaminergic depletion. OBJECTIVES To study the effect of two doses of pramipexole (PPX) on motor impulsivity, delay intolerance and compulsive-like behaviour. METHODS Male rats with mild dopaminergic denervation in the dorsolateral striatum (bilateral injections of 6-hydroxidopamine (6-OHDA)) treated with two doses of PPX (0.25 mg/kg and 3 mg/kg) and tested in the variable delay-to-signal paradigm. RESULTS Partial (50%) dopaminergic depletion did not induce significant changes in motor impulsivity or delay intolerance. However, 0.25 mg/kg of PPX increased motor impulsivity, while 3 mg/kg of PPX increased both motor impulsivity and delay intolerance. These effects were independent of the drug's antiparkinsonian effects. Importantly, impulsivity scores before and after dopaminergic lesion were positively associated with the impulsivity observed after administering 3 mg/kg of PPX. No compulsive-like behaviour was induced by PPX administration. CONCLUSIONS We described a rat model, with a moderate dorsolateral dopaminergic lesion resembling that suffered by patients with early PD, that develops different types of impulsivity in a dose-dependent manner dissociated from motor benefits when treated with PPX. This model recapitulates key features of abnormal impulsivity in PD and may be useful for deepening our understanding of the pathophysiology of ICD.

中文翻译：

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用帕金森病大鼠中的多巴胺能激动剂以剂量依赖的方式引起运动冲动和延迟不耐受。

原理多巴胺能激动剂治疗的帕金森氏病（PD）患者中经常发现冲动控制障碍（ICD）和其他冲动-强迫行为。迄今为止，尚无可用的动物模型来研究其病理生理学并确定是否可以通过改变剂量的多巴胺能药物来诱发它们。此外，关于纹状体多巴胺能消耗的易感性模式还存在一些争议。目的研究两种剂量的普拉克索（PPX）对运动冲动性，延迟不耐性和强迫性行为的影响。方法雄性大鼠背外侧纹状体轻度多巴胺能神经支配（双侧注射6-羟基氧化胺（6-OHDA））用两种剂量的PPX（0.25 mg / kg和3 mg / kg）进行治疗，并测试可变延迟时间信号范式。结果部分（50％）的多巴胺能消耗并未引起运动冲动的明显改变或延迟不耐受。但是，0.25 mg / kg的PPX增加运动冲动，而3 mg / kg的PPX增加运动冲动和延迟不耐性。这些作用与药物的抗帕金森病作用无关。重要的是，多巴胺能病变之前和之后的冲动评分与服用3 mg / kg PPX后观察到的冲动呈正相关。PPX给药未引起强迫性行为。结论我们描述了一种大鼠模型，该模型具有与早期PD患者相似的中度背外侧多巴胺能性病变，当用PPX治疗时，它以剂量依赖性方式发展出不同类型的冲动，而与运动益处无关。