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首页> 外文期刊>The European Journal of Neuroscience >Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcohol.
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Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcohol.

机译：反复戒酒后，恐惧适应能力下降，但癫痫发作敏感性增强。

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Repeated experience of withdrawal from chronic alcohol treatment increases sensitivity to seizures. It has been argued by analogy that negative affective consequences of withdrawal also sensitize, but repeated experience of withdrawal from another sedative-hypnotic drug, diazepam, results in amelioration of withdrawal anxiety and aversiveness. We tested whether giving rats repeated experience of withdrawal from alcohol altered their ability to acquire a conditioned emotional response (CER). Male Hooded Lister rats were fed a nutritionally complete liquid diet as their only food source. Different groups received control diet, or diet containing 7% ethanol. Rats receiving ethanol diet were fed for either 24 days (Single withdrawal, SWD), or 30 days, with two periods of 3 days, starting at day 11, and 21, in which they received control diet (Repeated withdrawal, RWD). All rats were fed lab chow at the end of their liquid diet feeding period. Starting 12 days after the final withdrawal, groups of Control, SWD and RWD rats were given pentylenetetrazole (PTZ; 30 mg/kg, i.p.) three times a week, and scored for seizures. The occurrence of two successive Stage 5 seizures was taken as the criterion for full PTZ kindling. Other groups of control, SWD and RWD rats were trained to operate levers to obtain food, and were then exposed, in a fully counterbalanced design, to light and tone stimuli which predicted unavoidable footshock (CS+), or which had no consequences (CS-). Rats consumed approximately 17.5 g/kg/day of ethanol, resulting in blood alcohol levels of approximately 100 mg/dL. Repeated administration of PTZ resulted in increasing seizure scores. RWD rats achieved kindling criterion faster than either Control or SWD rats. No differences were seen in the groups in flinch threshold to footshock (0.3 mA). At a shock intensity of 0.35 mA, Control, but not RWD or SWD rats showed significant suppression to the CS+ CS- presentation did not affect response rates. The three groups differed in their response to pairing the CS+ with increasing shock levels, the Controls remaining more sensitive to the CS+. SWD rats showed significant suppression of lever pressing during CS+ presentations only at 0.45 and 0.5 mA, and RWD rats only at 0.5 mA. Giving rats repeated experience of withdrawal from chronic ethanol results in increased sensitivity to PTZ kindling, but reduces their ability to acquire a CER. Withdrawal kindling of sensitivity to anxiogenic events does not seem to occur under circumstances which give rise to kindling of seizure sensitivity.
机译：反复戒酒的经验增加了对癫痫发作的敏感性。类推认为，戒断的负面情感影响也很敏感，但是从另一种镇静催眠药地西epa中反复戒断的经验可减轻戒断焦虑和厌恶感。我们测试了给予大鼠反复戒酒的经历是否会改变其获得条件性情绪反应（CER）的能力。给雄性连帽李斯特犬大鼠喂食完全营养的流质饮食，作为其唯一的食物来源。不同组接受对照饮食或含7％乙醇的饮食。从第11天和第21天开始，接受乙醇饮食的大鼠喂食24天（单次戒断，SWD）或30天，分为两个三天，分别接受控制饮食（重复戒断，RWD）。在流质饮食喂养期结束时，给所有大鼠喂实验室食物。在最后一次戒断后的12天开始，对对照组，SWD和RWD大鼠进行每周3次戊戊四唑（PTZ; 30 mg / kg，腹腔注射）的评分，并为癫痫发作评分。两次连续的5期癫痫发作的发生被视为完全PTZ点燃的标准。对其他组的对照组，SWD和RWD大鼠进行了训练以操作杠杆以获取食物，然后以完全平衡的设计暴露于预示不可避免的足部震荡（CS +）或没有后果的轻度和音调刺激中（CS- ）。大鼠消耗约17.5 g / kg /天的乙醇，导致血液中的酒精含量约为100 mg / dL。重复施用PTZ导致癫痫发作评分增加。 RWD大鼠比对照组或SWD大鼠更快地达到点燃标准。各组在脚颤的阈值（0.3 mA）方面均未见差异。在0.35 mA的电击强度下，对照组（而非RWD或SWD）显示出对CS + CS呈递的显着抑制，但不影响反应率。这三组对CS +与不断增加的电击水平配对的反应有所不同，对照组仍然对CS +更为敏感。在CS +演示中，SWD大鼠仅在0.45和0.5 mA时显示出明显的杠杆压制抑制，而RWD大鼠仅在0.5 mA时显示出显着抑制。给大鼠反复退出慢性乙醇的经历会提高对PTZ点燃的敏感性，但会降低其获得CER的能力。在引起癫痫发作敏感性的情况下，似乎没有发生对焦虑发生事件的敏感性退缩。

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