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自愿饮酒对撒丁岛酒精偏好大鼠中枢杏仁核中促肾上腺皮质释放因子和前强啡肽 mRNA 水平的影响。

Effects of voluntary alcohol drinking on corticotropin-releasing factor and preprodynorphin mRNA levels in the central amygdala of Sardinian alcohol-preferring rats.

机构信息

Laboratory of the Biology of Addictive Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.

出版信息

Neurosci Lett. 2013 Oct 25;554:110-4. doi: 10.1016/j.neulet.2013.08.071. Epub 2013 Sep 8.

Abstract

The stress-response corticotropin-releasing factor (CRF) and dynorphin systems are critically involved in alcohol drinking and "anxiety"-related behaviors. Selectively bred Sardinian alcohol-preferring (sP) rats display high inherent "anxiety"-related behaviors, in comparison with their alcohol-nonpreferring counterpart (sNP rats). The present study was undertaken to investigate: (1) if there were genetically determined differences in basal gene expression levels of CRF, CRF-R1, preprodynorphin (ppDyn) and kappa opioid receptor (KOP-r) between sP and sNP rats; specifically, mRNA levels of the above genes were measured in the central amygdala (CeA), hypothalamus and other stress responsive and mesolimbic regions of alcohol-naive sP and sNP rats; and (2) if the above mRNA levels were altered by voluntary alcohol drinking in sP rats exposed to the standard, homecage 2-bottle "alcohol vs. water" choice regimen 24h/day for 17 days. Higher basal CRF mRNA levels were found only in CeA of alcohol-naive sP rats, compared with sNP rats; these levels were decreased after alcohol consumption. In contrast, ppDyn mRNA levels in CeA of sP rats were increased by alcohol consumption, but with no basal difference from sNP rats. Although higher basal ppDyn mRNA levels were found in hypothalamus of sP rats, compared with sNP rats, there was no alteration after alcohol drinking in sP rats. No difference for the above mRNA levels was observed in other regions, including nucleus accumbens shell or core, caudate-putamen, ventral tegmental area and medial/basolateral amygdala, between the two rat lines before or after alcohol consumption. Our results demonstrate the existence of genetically determined high basal CRF mRNA levels in CeA of sP rats. Alcohol consumption decreased CeA CRF mRNA levels with parallel increases in CeA ppDyn mRNA levels.

摘要

应激反应促肾上腺皮质释放因子(CRF)和强啡肽系统在酒精摄入和“焦虑”相关行为中起着至关重要的作用。与它们的酒精非偏好(sNP)大鼠相比,选择性繁殖的撒丁岛酒精偏好(sP)大鼠表现出高的固有“焦虑”相关行为。本研究旨在探讨:(1)sP 和 sNP 大鼠之间是否存在 CRF、CRF-R1、前强啡肽(ppDyn)和κ阿片受体(KOP-r)的基础基因表达水平的遗传差异;特别是,在酒精未处理的 sP 和 sNP 大鼠的中央杏仁核(CeA)、下丘脑和其他应激反应和中脑边缘区域测量了上述基因的 mRNA 水平;(2)如果 sP 大鼠在暴露于标准、家庭笼 2 瓶“酒精与水”选择方案 24 小时/天的情况下自愿饮酒 17 天,上述 mRNA 水平是否会发生改变。与 sNP 大鼠相比,在酒精未处理的 sP 大鼠的 CeA 中仅发现更高的基础 CRF mRNA 水平,这些水平在饮酒后降低。相反,在 sP 大鼠的 CeA 中,ppDyn mRNA 水平在饮酒后增加,但与 sNP 大鼠相比没有基础差异。尽管与 sNP 大鼠相比,sP 大鼠的下丘脑中有更高的基础 ppDyn mRNA 水平,但在 sP 大鼠饮酒后没有改变。在酒精处理前后,两个大鼠系之间在其他区域(包括伏隔核壳或核、尾壳核、腹侧被盖区和内侧/基底杏仁核)也没有观察到上述 mRNA 水平的差异。我们的结果表明,sP 大鼠的 CeA 中存在遗传决定的高基础 CRF mRNA 水平。酒精摄入降低了 CeA CRF mRNA 水平,同时 CeA ppDyn mRNA 水平平行增加。

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