慢性酒精中毒大鼠脑组织中第二型食欲素受体(ORXR2) mRNA水平的变化

E. Sekste, M. Airapetov, S. Eresko, E. Bychkov, A. Lebedev, G. P. Kosyakova, P. Shabanov
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摘要

背景:食欲素及其受体参与了病理性嗜酒的机制,但对于酒精成瘾条件下大鼠大脑中OX2R基因的表达尚无明确的答案。目的:本研究的目的是测定长时间酒精中毒和戒酒期间大鼠脑结构中OX2R mRNA的水平。材料与方法:以15%乙醇为唯一液源,对成年雄性Wistar大鼠进行酒精处理6个月。在慢性酒精中毒后以及戒酒第1天和第7天对大鼠进行斩首。脑结构样品(前额皮质、海马、腹侧被盖区)冷冻于液氮中,80℃保存。采用pcr法测定OX2R mRNA水平。结果:戒断第7天海马组织中ORXR2基因表达水平较正常组和慢性酒精中毒组显著升高。戒酒动物组(第1和第7天)的前额叶皮层和腹侧被盖区OX2R mRNA水平与酒精和正常动物无关。结论:食欲素脑系统可能是预防酒精戒断复发的一个新的潜在治疗靶点。结合先前获得的数据,可以得出结论,食欲素受体拮抗剂可以用来减少病理性的酒精渴望。
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Level of mRNA of orexin receptors of second type (ORXR2) in conditions of chronic alcoholation in structures of the rat brain
BACKGROUND: Orexin and its receptors are involved in the mechanisms of pathological craving for alcohol, but there is no unambiguous answer about the expression of the OX2R gene in the rat brain under conditions of alcohol addiction. AIM: The aim of this study was to determine the level of OX2R mRNA in brain structures in rats under conditions of prolonged alcoholization and during the period of abstinence. MATERIALS AND METHODS: Adult male Wistar rats were alcoholized with 15% ethanol as the only source of liquid for 6 months. The rats were decapitated after chronic alcoholization, as well as on the 1st and 7th days of alcohol withdrawal. Samples of brain structures (prefrontal cortex, hippocampus, ventral tegmental area) were frozen in liquid nitrogen and stored at 80C. Determination of the level of OX2R mRNA was carried out using the method of PCR-analysis. RESULTS: The level of ORXR2 gene expression significantly increased in the hippocampus on the 7th day of abstinence in relation to the group of intact animals and in relation to the group of chronically alcoholized rats. The level of OX2R mRNA in the prefrontal cortex and ventral tegmental area in animal groups of abstinence (1st and 7th days) did not change in relation to both alcohol and the intact animals. CONCLUSIONS: It is concluded that the orexin brain system may represent a new potential therapeutic target for the prevention of relapse in alcohol withdrawal. Together with the previously obtained data it was concluded that orexin receptor antagonists can be used to reduce the pathological craving for alcohol.
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