CHARACTERIZATION OF A THIAMINE DEFICIENCY MODEL OF KORSAKOFF'S PSYCHOSIS

用硫胺素缺乏（TD）饮食处理的Sprague-Dawley大鼠出现了一种 行为和神经病理学上类似韦尼克氏综合征 脑病（Korsakoff精神病的急性期）。 大鼠表现出 TD综合征在腹膜内注射后数小时内行为改善 注射硫胺素; 2-3个月后，他们的体重相同，似乎没有 与对照动物不同。 两种性别的哺乳动物（至少 TD后6个月）对以下因素的影响明显不那么敏感 酒精作为衡量行为障碍和体温过低，也许是由于 增加酒精代谢和/或降低CNS敏感性。 因此，我们认为， TD可能有助于药代动力学和药效学耐受性 慢性酒精中毒者中观察到的酒精 初步调查结果表明 在缺乏硫胺素的大鼠中也可能存在类似的现象 在子宫里 由于发展综合征所需的时间， TD在远交品系中变化很大，我们评价了10个近交品系， 评价了10个近交系大鼠品系，以确定它们对TD的敏感性。 一 筛选出对TD敏感的菌株（M520）和对TD抗性的菌株（F344 以供进一步研究。 M520大鼠乙醇代谢更快， 在同等血液乙醇水平（BEC）下受损， 在自由选择（乙醇溶液/水）范例中，乙醇的浓度增加了10-15倍 F344大鼠 M520大鼠的过氧化氢酶活性更高，但肝脏 乙醇脱氢酶（ADH）活性无显著差异。 TD 7周后，M520大鼠的基线体重下降更快， 与同品系对照组大鼠相比， 两 在TD过程中，菌株的肝脏ADH增加了两倍，但没有 过氧化氢酶的显着变化，与相同的对照组相比， 菌株

Sprague-Dawley rats treated with a thiamine-deficient (TD) diet develop a syndrome that behaviorally and neuropathologically resembles Wernicke's encephalopathy (the acute phase of Korsakoff's psychosis). Rats exhibiting the syndrome of TD improve behaviorally within hours after intraperitoneal injection of thiamine; after 2-3 months, they weigh the same and appear no different from control animals. Recovered animals of both sexes (at least 6 months post-TD) are significantly less sensitive to the effects of ethanol as measured by behavioral impairment and hypothermia, perhaps due to increased alcohol metabolism and/or reduced CNS sensitivity. Therefore, TD may contribute to both the pharmacokinetic and pharmacodynamic tolerance to alcohol observed in chronic alcoholics. Preliminary findings suggest that a similar phenomenon may be operative in rats made thiamine-deficient in utero. Since the duration of time required to develop the syndrome of TD varies greatly in outbred strains, we evaluated 10 inbred strains, we evaluated 10 inbred rat strains to determine their sensitivities to TD. A TD-sensitive strain (M520) and a TD-resistant strain (F344) were selected for further study. M520 rats metabolized ethanol more rapidly, were less impaired at equivalent blood ethanol levels (BEC), and preferred and drank 10-15 times more ethanol in a free-choice (ethanol solution/water) paradigm than F344 rats. Catalase activity was greater in M520 rats, but liver alcohol dehydrogenase (ADH) activities were not significantly different. After 7 weeks of TD, M520 rats showed a geater reduction of baseline body temperature and peak BEC than control rats of the same strain. Both strains showed a twofold increase in liver ADH during TD, but no significant change in catalase, compared with control rats of the same strains.