Universidade Regional Integrada do Alto Uruguai e das Missões-Campus Santiago, Santiago, RS, Brazil.
Eur J Pharmacol. 2013 Feb 15;701(1-3):65-72. doi: 10.1016/j.ejphar.2013.01.007. Epub 2013 Jan 20.
The present study was designed to examine the correlations between behavioural and oxidative parameters in a quinolinic acid model of Huntington's disease in rats. The protective effect of melatonin against the excitotoxicity induced by quinolinic acid was investigated. Rats were pre-treated with melatonin (5 or 20mg/kg) before injection of quinolinic acid (240nmol/site; 1μl) into their right corpora striata. The locomotor and exploratory activities as well as the circling behaviour were recorded. The elevated body swing test was also performed. After behavioural experiments, biochemical determinations were carried out. Melatonin partially protected against the increase of circling behaviour caused by quinolinic acid injection. No alteration was found in the number of crossings and rearings of animals treated with melatonin and/or quinolinic acid. Melatonin decreased the percentage of contralateral biased swings induced by quinolinic acid. Melatonin protected against the increase in reactive species and protein carbonyl levels as well as the inhibition of superoxide dismutase activity resulting from quinolinic acid injection. Melatonin was partially effective against the inhibition of striatal catalase activity and a decrease of non-protein thiol levels induced by quinolinic acid. Melatonin was not effective against the inhibition of Na(+), K(+) ATPase activity caused by quinolinic acid injection. There were significant correlations between circling behaviour and oxidative parameters. The antioxidant property of melatonin is involved, at least in part, in its neuroprotective effect. The results reinforce the idea that melatonin could be useful in overwhelming neurotoxicity caused by quinolinic acid, a rat model of Huntington's disease.
本研究旨在探讨在大鼠亨廷顿病喹啉酸模型中行为和氧化参数之间的相关性。研究了褪黑素对喹啉酸诱导的兴奋性毒性的保护作用。大鼠在右侧纹状体注射喹啉酸（240nmol/部位；1μl）前，用褪黑素（5 或 20mg/kg）预处理。记录运动和探索性活动以及转圈行为。还进行了高架体摆动试验。行为实验后，进行生化测定。褪黑素部分保护了喹啉酸注射引起的转圈行为增加。用褪黑素和/或喹啉酸处理的动物的穿越和后肢次数没有变化。褪黑素降低了喹啉酸诱导的对侧偏向摆动的百分比。褪黑素可防止因喹啉酸注射引起的活性物质和蛋白质羰基水平升高以及超氧化物歧化酶活性抑制。褪黑素对喹啉酸诱导的纹状体过氧化氢酶活性抑制和非蛋白巯基水平降低有一定的保护作用。褪黑素对喹啉酸注射引起的 Na(+)，K(+)ATP 酶活性抑制无作用。转圈行为与氧化参数之间存在显著相关性。褪黑素的抗氧化特性至少部分参与了其神经保护作用。这些结果增强了这样一种观点，即褪黑素可能对减轻喹啉酸引起的神经毒性有用，喹啉酸是亨廷顿病大鼠模型。
