酒精依赖大鼠戒断行为与血浆ACTH、皮质醇含量变化的观察

目的·· :研究慢性酒精刺激和戒断大鼠血浆促肾上腺皮质激素(ACTH)、皮质醇与其相关行为变化的关系 ,同时观察纳洛酮翻转作用。方法·· :给大鼠自由饮酒28d ,观察对照组、饮酒组及纳洛酮治疗组的戒断症状、游泳时间 ;利用放射免疫分析法检测血浆中ACTH、皮质醇水平。结果·· :饮酒组戒断2 -48h戒断症状评分均明显比对照组高,以戒断6h评分最高(16.5±s3.12,P<0.01),其游泳时间在戒断6h为22.8min±s4.2min ,与对照组比显著延长(P<0.01) ;饮酒28d及戒断后血浆皮质醇水平渐升高,在戒断6h达最高(17.03ng·ml-1±s3.9ng·ml-1) ,至72h时降至正常水平 ;而血浆ACTH水平在饮酒28d及戒断后4h、24h显著降低 ,48h、72h逐渐恢复正常水平。纳洛酮治疗组与饮酒组比 ,戒断症状评分明显降低 ,游泳时间显著缩短 ,血浆皮质醇水平亦明显降低 ;但ACTH水平与饮酒组比较无显著性差异。结论·· :慢性酒精刺激及戒断导致垂体 -肾上腺轴功能紊乱 ,纳洛酮能阻止皮质醇的升高 ,减轻酒精戒断症状。

OBSERVATION ON CHANGES OF WITHDRAWAL BEHAVIORS AND ACTH, CORTISON LEVELS OF PLASMA IN ALCOHOL DEPENDENT RATS

Objective: To investigate the relations between the changes of ACTH, cortison levels in plasma and the changes of withdrawal behaviors after ethanol withdrawal and the reversal effects of naloxone on the changes induced by ethanol. Methods: Rats were administered water containing 6% ethanol(v/v) for 28 days to set up alcohol dependence model. After 3 weeks of ethanol administration, the rats were divided into two groups: ethanol administration group(continued to use ethanol), and naloxone treatment group(used ethanol at the same time). 22 rats used water as normal control. Withdrawal symptoms and swimming time were observed after ethanol withdrawal. Plasma ACTH and cortison were analyzed with radioimmunity analysis. Results: The withdrawal syndrome scores of ethanol administration group during 2-48 hours after ethanol withdrawal were obviously higher than those of the normal control group, the highest scores(16.5±s 3.12) obtained 6 hours after withdrawal. The ethanol administration group swam 22.8 min±s 4.2 min 6 hours after ethanol withdrawal, which was also longer than the normal control group did. Chronic ethanol administration and withdrawal leads to a significant increase of cortison in plasma, the highest level occurred 6 hours after ethanol withdrawal and it did not revert to normal level until 72 hours after ethanol withdrawal. The level of ACTH obviously decreased during chronic ethanol administration and 4 to 24 hours after ethanol withdrawal, and it did not rise to normal level until 48 hours, or 72 hours after ethanol withdrawal. The withdrawal syndrome scores obtained by naloxone treated group were obviously lower, the swimming time was significantly shortened and the cortison level was also significantly decreased compared with ethanol administration group. However naloxone had no effect on changes of ACTH. Conclusion: Pituitary-adrenal systems were severely disturbed during chronic ethanol exposure and ethanol withdrawal. Naloxone can reverse the increase in cortison of plasma, which may be part of the reasons for its reduction of withdrawal syndromes.