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Arachidonyl-2'-chloroethylamide (ACEA), a synthetic agonist of cannabinoid receptor, increases CB1R gene expression and reduces dyskinesias in a rat model of Parkinson's disease.
Pharmacology Biochemistry and Behavior ( IF 3.3 ) Pub Date : 2020-05-12 , DOI: 10.1016/j.pbb.2020.172950
Melissa Leija-Salazar 1 , Mario Bermúdez de León 2 , Azucena González-Horta 1 , Brenda González-Hernández 1
Affiliation  

l-Dopa is the most effective drug used for Parkinson's disease (PD), but after long-term treatment, the vast majority of PD patients develop abnormal involuntary movements (AIMs) termed l-Dopa-induced dyskinesia (LID). Cannabinoid receptors in the basal ganglia can modulate motor functions, but their role in the treatment of LID is controversial. Therefore, the aim of this study is to evaluate the motor behavior and mRNA expression of the cannabinoid receptor-1 (CB1R), encoded by the Cnr1 gene, in the striatum and globus pallidus of a 6-hydroxydopamine rat model of PD. The evaluated rats had 6-hydroxydopamine-induced injury, LID, and LID treated with arachidonyl-2′-chloroethylamide (ACEA), a cannabinoid receptor agonist. Contralateral turns and AIMs were recorded to assess motor behavior. Gene expression was quantified by reverse transcription coupled with quantitative polymerase chain reaction using TaqMan probes. Behavioral evaluations demonstrated that dyskinetic rats treated with ACEA had a significant reduction in AIMs compared to the dyskinetic group. The expression of CB1R mRNA was significantly decreased in the 6-hydroxydopamine-injured and dyskinetic rats, compared to intact rats. The striata of dyskinetic rats treated with ACEA exhibited highly significant increases in CB1R mRNA expression. Contrary to results in the striatum, a lower CB1R expression was observed in globus pallidus from dyskinetic ACEA-treated group. In summary, significant differences in mRNA expression of CB1R were found between the evaluated groups of rats, suggesting the occurrence of compensatory mechanisms that may result in the ACEA-mediated reduction of dyskinesias in a rat model of PD.



中文翻译:

大麻素受体的合成激动剂花生四基-2'-氯乙酰胺(ACEA)在帕金森氏病大鼠模型中增加CB1R基因表达并减少运动障碍。

1- Dopa是用于治疗帕金森氏病(PD)的最有效药物,但经过长期治疗,绝大多数PD患者会出现异常的非自愿运动(AIM),称为1 -Dopa引起的运动障碍(LID)。基底神经节中的大麻素受体可以调节运动功能,但它们在LID治疗中的作用尚有争议。因此,本研究的目的是评估由Cnr1编码的大麻素受体1(CB 1 R)的运动行为和mRNA表达基因在PD的6-羟基多巴胺大鼠模型的纹状体和苍白球中。评估的大鼠具有6-羟基多巴胺诱导的损伤,LID和用大麻素受体激动剂花生四烯酸-2'-氯乙酰胺(ACEA)处理的LID。记录对侧转弯和AIM以评估运动行为。使用TaqMan探针通过逆转录结合定量聚合酶链反应对基因表达进行定量。行为评估表明,与运动障碍组相比,接受ACEA治疗的运动障碍大鼠的AIM明显减少。与完整大鼠相比,在6-羟基多巴胺损伤和运动障碍的大鼠中,CB 1 R mRNA的表达显着降低。用ACEA治疗的运动障碍大鼠纹状体的CB高度增加1 R mRNA表达。与纹状体的结果相反,在运动障碍ACEA治疗组的苍白球中观察到较低的CB 1 R表达。总之,在所评估的大鼠组之间发现了CB 1 R mRNA表达的显着差异,表明补偿机制的出现可能导致ACEA介导的PD大鼠模型运动障碍减少。

更新日期:2020-05-12
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