Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats
Corticotropin-releasing factor within the central nucleus of the amygdala mediates enhanced ethanol self-administration in withdrawn, ethanol-dependent rats
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DOI：
10.1523/jneurosci.3096-06.2006
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发表时间：
2006-11-01
影响因子：
5.3
通讯作者：
Koob, George F.
中科院分区：
文献类型：
--
作者：
Funk, Cindy K.;O'Dell, Laura E.;Koob, George F.
酒精依赖的特征是过度饮酒，对摄取失去控制，并出现戒断综合征，包括动机和身体症状。包括焦虑在内的动机症状一直被认为是导致禁欲期间过度饮酒的重要因素。先前的工作表明，酒精依赖大鼠在戒断过程中也表现出类似焦虑的行为和增强的酒精自我给药，这可能是由于大脑促肾上腺皮质激素释放因子(CRF)应激系统的失调所致。本研究旨在探讨延展杏仁核[杏仁中央核(CEA)、终纹外侧床核(BNST)和伏隔核壳核(NAcSh)]内与戒断过程中观察到的酒精自我给药增加有关的脑部位。与非依赖对照组相比，酒精依赖动物在急性戒断后的乙醇自我给药增加。将CRF拮抗剂D-Phe-CRF12-41([D-Phe(12)，NLE(21，38)，CαMeLeu(37)]-rCRF((12-41)注入急性戒断依赖和非依赖大鼠的CEA、外侧BNST或NAcSh。给予CEA，该拮抗剂减少依赖动物的乙醇自身给药，而对非依赖动物没有影响。在依赖和非依赖动物的BNST和NAcSh外侧注射D-Phe-CRF12-41对乙醇自身给药无影响。在戒断的同一时间点，CEA内CRF免疫反应性下降，提示在戒断过程中细胞外CRF释放增加。BNST和NAcSh的CRF免疫反应性无明显变化。这些结果表明，CRF，特别是在CEA内，在调节乙醇依赖动物过度的乙醇消耗方面发挥了作用。
Alcohol dependence is characterized by excessive consumption, loss of control over intake, and the presence of a withdrawal syndrome, including both motivational and physical symptoms. The motivational symptoms, including anxiety, have been hypothesized to be important factors eliciting excessive drinking during abstinence. Previous work has shown that ethanol-dependent rats also display enhanced anxiety-like behaviors and enhanced ethanol self-administration during withdrawal, likely resulting from dysregulation of brain corticotropin-releasing factor (CRF) stress systems. The present study was designed to explore the brain sites within the extended amygdala [central nucleus of the amygdala (CeA), lateral bed nucleus of the stria terminalis (BNST), and nucleus accumbens shell (NAcSh)] that mediate the increased ethanol self-administration observed during withdrawal. Ethanol-dependent animals showed an increase in ethanol self-administration after acute withdrawal relative to nondependent controls. The CRF antagonist D-Phe-CRF12-41 ([D-Phe(12), Nle(21,38), C alpha MeLeu(37)]-rCRF((12-41))) was administered into the CeA, lateral BNST, or NAcSh of acute-withdrawn dependent and nondependent rats. Administered into the CeA, the antagonist reduced ethanol self-administration in dependent animals, with no effect in nondependent animals. Administration of D-Phe-CRF12-41 into the lateral BNST and NAcSh was without effect on ethanol self-administration in dependent and nondependent animals. At the same time point of withdrawal, there was a decrease in CRF immunoreactivity within the CeA, suggesting an increased extracellular release of CRF during withdrawal. There was no change in CRF immunoreactivity in the BNST or NAcSh. These results indicate that CRF, specifically within the CeA, plays a role in mediating excessive ethanol consumption in ethanol-dependent animals.