Corticotropin-releasing factor gene expression is down-regulated in the central nucleus of the amygdala of alcohol-preferring rats which exhibit high anxiety: a comparison between rat lines selectively bred for high and low alcohol preference

Corticotropin-releasing factor gene expression is down-regulated in the central nucleus of the amygdala of alcohol-preferring rats which exhibit high anxiety: a comparison between rat lines selectively bred for high and low alcohol preference
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DOI:
10.1016/j.brainres.2004.08.042
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发表时间:
2004-11-05
期刊:
影响因子:
2.9
通讯作者:
Li, TK
Li, TK
中科院分区:
医学3区
文献类型:
--
作者:
Hwang, BH;Stewart, R;Li, TK

文献摘要

被引文献

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杏仁体促肾上腺皮质激素释放因子(CRF)在酒精中毒中的作用尚不清楚。酒精偏好(alcohol-prefering,P)大鼠和高度酒精饮用(high alcohol-drinking,HAD)大鼠被选择性地饲养以获得高度酒精偏好,并且被认为是研究酒精中毒的合适动物模型。本实验观察了P大鼠和HAD大鼠杏仁核中央核(CeA)CRF神经元的分布,并与不喜欢饮酒(NP)大鼠和低饮酒(LAD)大鼠作了比较。具体而言,CRF免疫反应(ir)在CeA和室旁下丘脑室核(PVN)进行了评估,使用放射免疫组织化学(RIH)测定在酒精幼稚的P/NP大鼠,和HAD/LAD大鼠。此外,用原位杂交法检测P/NP大鼠CeA中CRF mRNA的表达。还使用高架十字迷宫评估焦虑水平。本研究结果表明,CRF-ir在P大鼠的CeA显著低于NP大鼠。此外,P大鼠CeA的CRF mRNA也明显低于NP大鼠。在PVN中未观察到此类差异。有趣的是,这些P大鼠表现出更高的焦虑比NP大鼠。而HAD和LAD大鼠的CEA和PVN的CRF-ir在焦虑水平相似的情况下无先天性差异。该研究与文献一致,文献显示CRF敲除(KO)诱导饮酒,CRF的中心给药减少了酒精摄入。总的来说,本研究表明,减少CRF基因表达的CeA的P大鼠与他们的酒精偏好和焦虑。(C)2004 Elsevier B. V.保留所有权利。
The role of amygdaloid corticotropin-releasing factor (CRF) in alcoholism is not clear. Alcohol-preferring (P) rats and high alcohol-drinking (HAD) rats are selectively bred for high alcohol preference, and have been considered suitable animal models for studying alcoholism. The CRF neurons in the central nucleus of the amygdala (CeA) of P rats and HAD rats were studied in comparison with those of their respective counterparts, namely, alcohol-nonpreferring (NP) rats and low alcohol-drinking (LAD) rats. Specifically, CRF-immunoreactivity (ir) in the CeA and paraventricular hypothalamic nucleus (PVN) was assessed using radiommumohistochemical (RIH) assay in alcohol-naive P/NP rats, and HAD/LAD rats. Furthermore, CRF mRNA was examined using in situ hybridization in the CeA of P/NP rats. Anxiety levels were also evaluated using an elevated plus maze. Results of the present study showed that CRF-ir was significantly lower in the CeA of P rats than NP rats. Moreover, CRF mRNA in the CeA was also much lower in P rats than NP rats. Such differences were not seen in the PVN. Interestingly, those P rats exhibited higher anxiety than NP rats. In contrary, there were no innate differences of CRF-ir in both the CeA and PVN between HAD and LAD rats whose anxiety levels were similar. This study is consistent with the literature showing CRF knockout (KO) induces alcohol drinking, and central administrations of CRF reduce alcohol intake. Collectively, the present study suggests that reduced CRF gene expression in the CeA of P rats is associated with their alcohol preference and anxiety. (C) 2004 Elsevier B.V. All rights reserved.