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Disturbances in behavior and cortical enkephalin gene expression during the anticipation of ethanol in rats characterized as high drinkers

机译:饮酒高的大鼠预期乙醇中行为和皮质脑啡肽基因表达的障碍

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The process of ethanol anticipation is a particularly important phenomenon that can determine subsequent drug-taking behavior. Recent studies suggest that systems within the medial prefrontal cortex (mPFC), during anticipation, may contribute to the goal-directed seeking of ethanol. The current investigation examined the possibility that the opioid peptide enkephalin (ENK), known to mediate some of the reinforcing properties of ethanol, may function in the mPFC during the anticipation of ethanol access. Using a limited access (3 h/d) paradigm for 10 days with 20% ethanol, Sprague-Dawley rats were first identified either as low drinkers (LD, <1.0 g/kg/3 h) or as high drinkers (HD, >2.0 g/kg/3 h) that exhibited a long-term phenotype of high ethanol consumption and a significant ethanol deprivation effect. During the anticipation period immediately preceding daily ethanol access, the HD rats compared to LD or Control animals with ad libitum ethanol access exhibited increased anticipatory behaviors, including greater exploratory behavior in a novel open field as revealed by significantly more time spent in the rearing position (+53-65%, p < 0.05) and increased number of rears made (+33-44%, p < 0.05) and greater novelty-seeking behavior in a hole-board apparatus revealed by an increase in total (+50-52%, p < 0.05) and novel nose pokes (+45-48%, p < 0.05). In the HD rats, analysis of the mPFC using real-time quantitative PCR showed significantly greater mRNA levels of ENK (p < 0.05) and the mu-opioid receptor (MOR) (p < 0.05), but not delta-opioid receptor (DOR), and this increase in ENK expression was found, using in situ hybridization, to occur specifically in the prelimbic (PrL) subregion of the mPFC. When injected into the PrL during the anticipation period, a MOR agonist but not DOR agonist significantly increased consumption of 20% ethanol (p < 0.05). These findings support the role of ENK, acting through MOR within the PrL to promote the anticipation and excessive consumption of ethanol.
机译:乙醇预期的过程是一个特别重要的现象,可以确定随后的吸毒行为。最近的研究表明,在预期过程中,内侧前额叶皮层(mPFC)内的系统可能有助于目标导向的乙醇寻找。当前的研究检查了已知介导乙醇某些增强特性的阿片肽脑啡肽(ENK)在预期进入乙醇期间可能在mPFC中起作用的可能性。使用限量访问(3 h / d)范例,在20天使用20%乙醇的情况下持续10天,首先将Sprague-Dawley大鼠识别为低酒量(LD,<1.0 g / kg / 3 h)或高酒量(HD,> 2.0 g / kg / 3 h)表现出高乙醇消耗的长期表型和明显的乙醇剥夺作用。在每日乙醇摄入前的预期期内,与自由摄入乙醇的LD或对照动物相比,HD大鼠表现出较高的预期行为,包括在新的空旷地中的较大探索行为,这表现为在饲养位置花费了更多时间( + 53-65%,p <0.05)和增加的后排次数(+ 33-44%,p <0.05),并且在洞洞板设备中寻求新奇行为的次数增加(总数增加+ 50-52) %,p <0.05)和新颖的鼻po(+ 45-48%,p <0.05)。在HD大鼠中,使用实时定量PCR对mPFC的分析显示,ENK和p阿片受体(MOR)的mRNA水平显着更高(p <0.05)(p <0.05),而δ阿片受体(DOR)却没有。 ),并且使用原位杂交发现ENK表达的这种增加特别发生在mPFC的前缘(PrL)子区域中。在预期期间将其注射到PrL中时,MOR激动剂而非DOR激动剂会显着增加20%乙醇的消耗(p <0.05)。这些发现支持ENK的作用,通过PrL中的MOR促进乙醇的预期和过度消耗。

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