Costa Priscila A, Poli Jefferson H Z, Sperotto Nathalia D M, Moura Dinara J, Saffi Jenifer, Nin Maurício S, Barros Helena M T
Laboratory of Neuropsycopharmacology, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, Rio Grande do Sul, Brazil.
Psychopharmacology (Berl). 2015 Oct;232(19):3623-36. doi: 10.1007/s00213-015-4015-x. Epub 2015 Aug 2.
Alcohol addiction causes severe problems, and its deprivation may potentiate symptoms such as anxiety. Furthermore, ethanol is a neurotoxic agent that induces degeneration and the consequences underlying alcohol-mediated brain damage remain unclear.
This study assessed the behavioral changes during acute ethanol withdrawal periods and determined the levels of DNA damage and reactive oxygen species (ROS) in multiple brain areas.
Male Wistar rats were subjected to an oral ethanol self-administration procedure with a forced diet where they were offered 8% (v/v) ethanol solution for 21 days followed by five repeated 24-h cycles alternating between ethanol withdrawal and re-exposure. Control animals received an isocaloric control diet without ethanol. Behavioral changes were analyzed on ethanol withdrawal days in the open-field (OF) and elevated plus-maze (EPM) tests within the first 6 h of ethanol deprivation. The pre-frontal cortex, hypothalamus, striatum, hippocampus, and cerebellum were dissected for alkaline and neutral comet assays and for dichlorofluorescein ROS testing.
The repeated intermittent ethanol access enhanced solution intake and alcohol-seeking behavior. Decreased exploratory activity was observed in the OF test, and the animals stretched less in the EPM test. DNA single-strand breaks and ROS production were significantly higher in all structures evaluated in the ethanol-treated rats compared with controls.
The animal model of repeated intermittent ethanol access induced behavioral changes in rats, and this ethanol exposure model induced an increase in DNA single-strand breaks and ROS production in all brain areas. Our results suggest that these brain damages may influence future behaviors.
酒精成瘾会引发严重问题，而戒酒可能会加剧焦虑等症状。此外，乙醇是一种神经毒性剂，其诱导的退化以及酒精介导的脑损伤背后的机制仍不清楚。
本研究评估了急性乙醇戒断期间的行为变化，并确定了多个脑区的DNA损伤水平和活性氧（ROS）水平。
雄性Wistar大鼠接受口服乙醇自我给药程序并强制喂食，给予它们8%（v/v）乙醇溶液，持续21天，随后进行五个重复的24小时周期，在乙醇戒断和重新接触之间交替。对照动物接受不含乙醇的等热量对照饮食。在乙醇戒断的第1天，在乙醇剥夺的前6小时内，通过旷场（OF）试验和高架十字迷宫（EPM）试验分析行为变化。解剖前额叶皮质、下丘脑、纹状体、海马体和小脑，进行碱性和中性彗星试验以及二氯荧光素ROS检测。
重复间歇性接触乙醇增加了溶液摄入量和觅酒行为。在旷场试验中观察到探索活动减少，在高架十字迷宫试验中动物伸展次数减少。与对照组相比，乙醇处理大鼠的所有评估结构中的DNA单链断裂和ROS产生均显著更高。
重复间歇性接触乙醇的动物模型在大鼠中诱导了行为变化，并且这种乙醇暴露模型在所有脑区中诱导了DNA单链断裂和ROS产生的增加。我们的结果表明，这些脑损伤可能会影响未来的行为。
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