BACKGROUND As an atypical antipsychotic drug, quetiapine had been approved for bipolar disorder and for adjunctive therapy in major depressive disorder and schizophrenia. Recently quetiapine has been suggested to be a promising pharmacotherapy for alcohol dependence. This study was performed to determine the effects of quetiapine in rats chronically exposed to ethanol. METHODS Rats were exposed to ethanol solution (10 %; v/v) for 6 weeks. Saline or one of three doses of quetiapine (10, 20 or 40 mg/kg/day) was given by oral gavage while ethanol exposure for the next 14 weeks. Performance of learning and memory and withdrawal signs were evaluated. Then immunohistochemistry, western blot, quantitative real-time-PCR and transmission electron microscopy were performed to determine the effects of quetiapine on alterations of brain white matter markers (myelin basic protein, MBP; proteolipid protein, PLP) and morphology caused by chronic ethanol exposure. RESULTS Quetiapine treatment significantly alleviated withdrawal signs in the ethanol exposed rats. Chronic ethanol exposure reduced Y-type electric maze scores and the protein/mRNA expression levels of MBP and PLP in the prefrontal cortex and hippocampus, and these effects were reversed by quetiapine treatment. Similar ultrastructure morphological changes were observed. CONCLUSIONS Chronic quetiapine treatment alleviated the damage induced by chronic ethanol exposure with regard to learning and memory ability and to brain white matter. Thus, quetiapine appears to be a potentially promising pharmacotherapy for the treatment of alcohol use disorder.

中文翻译：

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喹硫平对慢性酒精依赖大鼠模型的行为变化和髓磷脂蛋白表达的影响。

背景技术喹硫平作为一种非典型的抗精神病药，已被批准用于双相情感障碍和重度抑郁症和精神分裂症的辅助治疗。最近，喹硫平已被提出是一种对酒精依赖的有前途的药物疗法。进行这项研究以确定喹硫平在长期暴露于乙醇的大鼠中的作用。方法大鼠暴露于乙醇溶液（10％； v / v）6周。在接下来的14周内，通过口服强饲法给予盐酸盐或三剂喹硫平（10、20或40 mg / kg /天）之一。评估学习记忆和退缩迹象的表现。然后进行免疫组化，蛋白质印迹，进行定量实时PCR和透射电镜观察，确定喹硫平对慢性乙醇暴露引起的脑白质标志物（髓鞘碱性蛋白，MBP，蛋白脂蛋白，PLP）变化和形态变化的影响。结果喹硫平治疗显着减轻了暴露于乙醇的大鼠的戒断症状。长期乙醇暴露降低了前额叶皮层和海马中Y型电迷宫评分以及MBP和PLP的蛋白质/ mRNA表达水平，喹硫平治疗可以逆转这些影响。观察到相似的超微结构形态变化。结论慢性喹硫平治疗减轻了慢性乙醇暴露对学习记忆能力和脑白质的损害。从而，