Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain
Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain
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DOI：
10.1111/j.1369-1600.2011.00326.x
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发表时间：
2013-05-01
影响因子：
3.4
通讯作者：
Romualdi, Patrizia
中科院分区：
文献类型：
--
作者：
D'Addario, Claudio;Caputi, Francesca F.;Romualdi, Patrizia
本文研究了酒精暴露对大鼠脑内阿片强啡肽和痛敏肽系统适应性改变的分子机制。将酒精灌胃给药于大鼠，类似于人类饮酒，暴露数小时：水或酒精（水中20%），剂量为1.5 g/kg，每日三次，持续1或5天。每天记录耐受性和依赖性的发展。在末次给药后30分钟（1天和5天组）或其他3个5天组（停药组）的1、3或7天解剖大脑。阿片样物质基因表达的特定改变被确定。在杏仁核中，在1天组中观察到前强啡肽和原阿片肽的上调;此外，5天组中的原阿片肽和κ阿片受体mRNA以及1天戒断组中的两种肽前体也上调。在前额叶皮层，在前强啡肽表达的增加，在1天组检测。这些数据表明，在与多重酒精暴露相关的负享乐状态的强啡肽能系统的相关作用。伤害感受素系统观察到的改变模式似乎与其对与其他阿片肽相关的乙醇作用的功能性拮抗作用一致。我们的研究结果可能有助于了解酒精如何差异影响大脑中的阿片系统，并建议强啡肽和痛敏素系统作为治疗和/或预防酒精依赖的可能靶点。
Molecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1- and 5-day groups) or 1, 3 or 7 days after the last administration for the three other 5-day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up-regulation of prodynorphin and pronociceptin was observed in the 1-day group; moreover, pronociceptin and the kappa opioid receptor mRNAs in the 5-day group and both peptide precursors in the 1-day withdrawal group were also up-regulated. In the prefrontal cortex, an increase in prodynorhin expression in the 1-day group was detected. These data indicate a relevant role of the dynorphinergic system in the negative hedonic states associated with multiple alcohol exposure. The pattern of alterations observed for the nociceptin system appears to be consistent with its role of functional antagonism towards the actions of ethanol associated with other opioid peptides. Our findings could help to the understanding of how alcohol differentially affects the opioid systems in the brain and also suggest the dynorphin and nociceptin systems as possible targets for the treatment and/or prevention of alcohol dependence.