Clermont Université, Université d'Auvergne, EA 7280, Clermont-Ferrand, France.
Neuropharmacology. 2013 Jul;70:74-82. doi: 10.1016/j.neuropharm.2012.12.011. Epub 2013 Jan 21.
Dopamine dysregulation syndrome in Parkinson's disease (PD) has been attributed to dopamine replacement therapy (DRT). We hypothesize that DRT can induce a potential rewarding effect in an animal model of PD. Using the conditioned place preference (CPP) paradigm, we investigated the motivational effects of L-dopa, dopamine receptor agonists (DRAs), and cocaine in rat with a bilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. In 6-OHDA animals, D1 receptors agonist (SKF81297) revealed significantly a conditioned place aversion (CPA) at 3 mg/kg and 9 mg/kg doses. D2 receptors agonist (bromocriptine) induced both CPP and CPA at 1 mg/kg and 10 mg/kg doses respectively. D3 receptors agonist (PD128907) induced a CPP only at 1 mg/kg, comparable to that of cocaine. Sham animals revealed biphasic CPP curves, with significant dose effect, for the intermediate dose of the 3 DRAs. However, L-dopa induced no significant effect while cocaine induced CPP in both lesioned and sham animals. In conclusion, this study confirms the predominant roles of D2R class, and most specifically D3R subtypes, in rewarding properties of DRT.
帕金森病（PD）中的多巴胺失调综合征归因于多巴胺替代疗法（DRT）。我们假设 DRT 可以在 PD 的动物模型中诱导潜在的奖励效应。使用条件位置偏好（CPP）范式，我们研究了 L-多巴、多巴胺受体激动剂（DRAs）和可卡因在双侧 6-OHDA 黑质纹状体多巴胺能通路损伤大鼠中的动机效应。在 6-OHDA 动物中，D1 受体激动剂（SKF81297）在 3 mg/kg 和 9 mg/kg 剂量下显著引起条件位置厌恶（CPA）。D2 受体激动剂（溴隐亭）分别在 1 mg/kg 和 10 mg/kg 剂量下诱导 CPP 和 CPA。D3 受体激动剂（PD128907）仅在 1 mg/kg 时诱导 CPP，与可卡因相当。假手术动物在 3 种 DRAs 的中间剂量下显示出双相 CPP 曲线，具有显著的剂量效应。然而，L-多巴没有引起显著的效果，而可卡因在损伤和假手术动物中都诱导 CPP。总之，这项研究证实了 D2R 类，特别是 D3R 亚型，在 DRT 的奖励特性中的主要作用。
