MICROINJECTION OF A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST INTO THE CENTRAL NUCLEUS OF THE AMYGDALA REVERSES ANXIOGENIC-LIKE EFFECTS OF ETHANOL WITHDRAWAL
MICROINJECTION OF A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST INTO THE CENTRAL NUCLEUS OF THE AMYGDALA REVERSES ANXIOGENIC-LIKE EFFECTS OF ETHANOL WITHDRAWAL
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DOI：
10.1016/0006-8993(93)91352-s
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发表时间：
1993-03-05
期刊：
影响因子：
2.9
通讯作者：
KOOB, GF
中科院分区：
文献类型：
--
作者：
RASSNICK, S;HEINRICHS, SC;KOOB, GF
先前的研究表明，自发探索“高架+迷宫”提供了一种敏感的“焦虑”测量方法，这种焦虑是由药理学或行为压力源引起的。特别是，在乙醇戒断期间，探索正迷宫张开臂的时间百分比减少，这种效果可以通过在脑室内给予25杯促肾上腺皮质激素释放因子拮抗剂α -螺旋CRF来拮抗（H.A. Baldwin等人，精神药理学，103(1991)227-232）。本研究旨在检测乙醇戒断期间杏仁核中央核内α -螺旋CRF输注的影响。通过维持含乙醇的液体饮食16天，使大鼠对乙醇产生依赖，并在乙醇进入后8小时退出乙醇，在升高+迷宫中进行测试。与成对喂养的对照大鼠相比，酒精戒断的实验对象花在探索正迷宫张开的双臂上的时间明显减少。向杏仁核中央核双侧注射250 ng α -螺旋CRF可拮抗这种打开臂探查的减少，但脑室内注射250 ng α -螺旋CRF不能拮抗这种减少。杏仁核内α -螺旋CRF对抗张开臂探索减少的能力不太可能是由于运动活动的变化，因为在所有EtOH戒断组中，迷宫的一般活动都减少了。这些结果表明，杏仁核中央核可能是内源性CRF系统介导与乙醇戒断相关的焦虑行为的有效部位。
Previous studies have shown that spontaneous exploration of the Elevated Plus Maze provides a sensitive measure of 'anxiety' induced by pharmacological or behavioral stressors. In particular, the percent time spent exploring the open arms of the plus maze is decreased during ethanol withdrawal, and this effect is antagonized by intracerebroventricular administration of 25 mug of alpha-helical CRF, a corticotropin-releasing factor antagonist (H.A. Baldwin et al., Psychopharmacology, 103 (1991) 227-232). The present study was designed to examine the effect of alpha-helical CRF infusion within the central nucleus of the amygdala during ethanol withdrawal. Rats were made dependent on ethanol by maintenance on an ethanol-containing liquid diet for 16 days, withdrawn from ethanol and tested on the elevated plus maze at 8 h post-ethanol access. In comparison with pair-fed control rats, ethanol withdrawn subjects spent significantly less percent time exploring the open arms of the plus maze. This decrease in open arm exploration was antagonized by administration of alpha-helical CRF (250 ng) bilaterally into the central nucleus of the amygdala, but not by intracerebroventricular administration of 250 ng of alpha-helical CRF. The ability of intra-amygdala alpha-helical CRF to antagonize decreased open arm exploration is unlikely to be due to changes in motor activity, since general activity on the maze was reduced in all EtOH withdrawal groups. These results suggest that the central nucleus of the amygdala may be an effective site for endogenous CRF systems to mediate anxious behavior associated with ethanol withdrawal.