CRF ANTAGONIST REVERSES THE ANXIOGENIC RESPONSE TO ETHANOL WITHDRAWAL IN THE RAT
CRF ANTAGONIST REVERSES THE ANXIOGENIC RESPONSE TO ETHANOL WITHDRAWAL IN THE RAT
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DOI：
10.1007/bf02244208
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发表时间：
1991-01-01
影响因子：
3.4
通讯作者：
BRITTON, KT
中科院分区：
文献类型：
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作者：
BALDWIN, HA;RASSNICK, S;BRITTON, KT
使用高架十字迷宫实验检测了神经肽促肾上腺皮质激素释放因子（CRF）在介导大鼠乙醇戒断行为效应中的作用。在实验1中，CRF（0.5微克，脑室内注射）减少了在高架十字迷宫开放臂上停留时间的百分比，这与“类焦虑”效应一致。CRF还减少了臂进入的总次数，表明总体活动减少。低剂量（5微克和25微克，脑室内注射）的CRF拮抗剂α - 螺旋CRF在高架十字迷宫中未产生行为效应，而较高剂量（50微克，脑室内注射）则引发了类似CRF的活性。在实验2中，大鼠用含乙醇（8.5 - 11.5%体积比）或蔗糖的液体食物维持2 - 3周。与从对照饮食中撤食的大鼠相比，从乙醇饮食中撤食8小时后，大鼠在高架十字迷宫中表现出“类焦虑”反应以及总体活动减少。α - 螺旋CRF显著拮抗了高架十字迷宫中乙醇戒断的“类焦虑”效应。总体活动以及乙醇戒断的体征，如尾巴僵硬、身体震颤和腹内侧远端弯曲，不受α - 螺旋CRF的影响。在撤去乙醇饮食后立即测定的血液酒精水平（BALs）显示，乙醇摄入量在各组之间没有差异。这些结果表明，中枢CRF系统活性的增加可能介导了乙醇戒断的焦虑效应。
The role of the neuropeptide corticotropin-releasing factor (CRF) in mediating the behavioral effects of ethanol withdrawal in the rat was examined using the elevated plus-maze test. In Experiment 1, CRF (0.5 mu-g ICV) reduced the percentage of time spent on the open arms of the elevated plus-maze, consistent with an "anxiogenic-like" effect. CRF also reduced the total number of arm entries, indicating a reduction in general activity. Low doses (5 and 25 mu-g ICV) of the CRF antagonist, alpha-helical CRF produced no behavioral effects in the elevated plus-maze, while a higher dose (50 mu-g ICV) elicited CRF-like activity. In experiment 2, rats were maintained for 2-3 weeks on a liquid diet containing ethanol (8.5-11.5% v/v) or sucrose. Eight hours after withdrawal from the ethanol diet rats displayed "anxiogenic-like" responses as well as a reduction in general activity in the elevated plus-maze compared with rats withdrawn from control diet. Alpha-helical CRF significantly antagonized the "anxiogenic-like" effects of ethanol withdrawal in the plus-maze. General activity and physical signs of ethanol withdrawal such as tail stiffness, body tremor and ventromedial distal flexion were unaffected by alpha-helical CRF. Blood Alcohol Levels (BALs) determined immediately after removal of the ethanol diet showed no group differences in ethanol consumption. These results suggest that increased activity of central CRF systems may mediate the anxiogenic effects of ethanol withdrawal.