Nordberg A, Wahlström G
Life Sci. 1982 Jul 19;31(3):277-87. doi: 10.1016/0024-3205(82)90590-2.
Rats were treated with ethanol in the drinking water for 73-75 weeks. The daily drinking periods were restricted to only 2x1 h to get significant ethanol blood concentrations. After the end of the ethanol treatment (last day of treatment denoted day 0 of the abstinence) tolerance to sedatives were recorded with a hexobarbital threshold method, convulsions recorded with jiggle cages, and muscarinic receptor binding sites determined with 3H-quinuclidinyl benzilate. Tolerance to hexobarbital was found to have a maximum on day 8 in the abstinence while convulsions recorded from the rats participating in the hexobarbital threshold determinations had a maximum on day 14. Atropine administered as a single dose on day 8 decreased the tolerance to hexobarbital on that day and seemed to reduce the number of convulsions on the following days. Muscarinic receptor sites were significantly increased in the striatum on day 8 of the abstinence at the time of maximal tolerance, This increase in muscarinic receptors was less in rats which had had convulsions during the abstinence before sacrifice. Thus the results indicate that cholinergic mechanisms are involved in the changes seen during the abstinence after chronic ethanol exposure.
大鼠饮用含乙醇的水73 - 75周。每日饮水时间限制为仅2×1小时，以获得显著的乙醇血药浓度。乙醇处理结束后（处理的最后一天记为戒断的第0天），用己巴比妥阈值法记录对镇静剂的耐受性，用抖动笼记录惊厥情况，并用3H - 喹核醇基苯甲酸酯测定毒蕈碱受体结合位点。发现对己巴比妥的耐受性在戒断第8天达到最大值，而参与己巴比妥阈值测定的大鼠记录的惊厥在第14天达到最大值。在第8天单次给予阿托品降低了当天对己巴比妥的耐受性，并且似乎减少了随后几天的惊厥次数。在耐受性最大时的戒断第8天，纹状体中的毒蕈碱受体位点显著增加。在处死前戒断期间发生惊厥的大鼠中，这种毒蕈碱受体的增加较少。因此，结果表明胆碱能机制参与了慢性乙醇暴露后戒断期间出现的变化。
