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促肾上腺皮质释放因子诱导的杏仁核γ-氨基丁酸释放在酒精依赖中起关键作用。

Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release plays a key role in alcohol dependence.

机构信息

Committee on the Neurobiology of Addictive Disorders, Scripps Research Institute, La Jolla, California 92037, USA.

出版信息

Biol Psychiatry. 2010 May 1;67(9):831-9. doi: 10.1016/j.biopsych.2009.11.007. Epub 2010 Jan 8.

DOI:10.1016/j.biopsych.2009.11.007
PMID:20060104
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2883449/
Abstract

BACKGROUND

Corticotropin-releasing factor (CRF) and gamma-aminobutyric acid (GABA)ergic systems in the central amygdala (CeA) are implicated in the high-anxiety, high-drinking profile associated with ethanol dependence. Ethanol augments CeA GABA release in ethanol-naive rats and mice.

METHODS

Using naive and ethanol-dependent rats, we compared electrophysiologic effects and interactions of CRF and ethanol on CeA GABAergic transmission, and we measured GABA dialyzate in CeA after injection of CRF(1) antagonists and ethanol. We also compared mRNA expression in CeA for CRF and CRF(1) using real-time polymerase chain reaction. We assessed effects of chronic treatment with a CRF(1) antagonist on withdrawal-induced increases in alcohol consumption in dependent rats.

RESULTS

CRF and ethanol augmented CeA GABAergic transmission in naive rats via increased GABA release. Three CRF1 receptor (CRF(1)) antagonists decreased basal GABAergic responses and abolished ethanol effects. Ethanol-dependent rats exhibited heightened sensitivity to CRF and CRF(1) antagonists on CeA GABA release. Intra-CeA CRF(1) antagonist administration reversed dependence-related elevations in GABA dialysate and blocked ethanol-induced increases in GABA dialyzate in both dependent and naive rats. Polymerase chain reaction studies indicate increased expression of CRF and CRF(1) in CeA of dependent rats. Chronic CRF(1) antagonist treatment blocked withdrawal-induced increases in alcohol drinking by dependent rats and tempered moderate increases in alcohol consumption by nondependent rats in intermittent testing.

CONCLUSIONS

These combined findings suggest a key role for specific presynaptic CRF-GABA interactions in CeA in the development and maintenance of ethanol dependence.

摘要

背景

促肾上腺皮质释放因子（CRF）和γ-氨基丁酸（GABA）能系统在中枢杏仁核（CeA）中与乙醇依赖相关的高焦虑、高饮酒特征有关。乙醇增强了乙醇-naive 大鼠和小鼠的 CeA GABA 释放。

方法

使用酒精-naive 和酒精依赖的大鼠，我们比较了 CRF 和乙醇对 CeA GABA 能传递的电生理效应和相互作用，并且在注射 CRF(1)拮抗剂和乙醇后测量了 CeA 中的 GABA 透析液。我们还使用实时聚合酶链反应比较了 CeA 中 CRF 和 CRF(1)的 mRNA 表达。我们评估了慢性 CRF(1)拮抗剂治疗对依赖大鼠戒断诱导的酒精消费增加的影响。

结果

CRF 和乙醇通过增加 GABA 释放来增强酒精-naive 大鼠的 CeA GABA 能传递。三种 CRF1 受体（CRF(1)）拮抗剂降低了基础 GABA 反应并消除了乙醇的作用。酒精依赖大鼠在 CeA 的 GABA 释放上表现出对 CRF 和 CRF(1)拮抗剂的更高敏感性。CeA 内 CRF(1)拮抗剂给药逆转了与依赖相关的 GABA 透析液升高，并阻断了依赖和酒精-naive 大鼠中乙醇诱导的 GABA 透析液升高。聚合酶链反应研究表明，依赖大鼠 CeA 中 CRF 和 CRF(1)的表达增加。慢性 CRF(1)拮抗剂治疗阻断了依赖大鼠戒断诱导的饮酒增加，并缓和了间歇性测试中不依赖大鼠的酒精消费的适度增加。

结论

这些综合发现表明，CeA 中特定的突触前 CRF-GABA 相互作用在乙醇依赖的发展和维持中起着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/0920c489f29c/nihms195789f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/1410007f8c27/nihms195789f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/bcb752dc73e2/nihms195789f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/2b46924e72a6/nihms195789f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/27c0a93d3ae6/nihms195789f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/0920c489f29c/nihms195789f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/1410007f8c27/nihms195789f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/bcb752dc73e2/nihms195789f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/2b46924e72a6/nihms195789f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/27c0a93d3ae6/nihms195789f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb1c/2883449/0920c489f29c/nihms195789f5.jpg

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