CHARACTERIZATION OF A THIAMINE DEFICIENCY MODEL OF KORSAKOFF'S PSYCHOSIS

用硫胺素缺乏(TD)饮食治疗的Spraogue-Dawley大鼠出现 行为和神经病理上类似韦尼克综合征的综合征 脑病(科萨科夫精神病的急性期)。大鼠表现出 TD综合征在腹膜腔内注射后数小时内行为改善 注射硫胺素；2-3个月后，它们的重量相同，看起来没有 与对照动物不同。回收的两性动物(至少 TD后6个月)对以下影响的敏感性显著降低 通过行为障碍和体温过低来衡量的酒精，可能是由于 增加酒精代谢和/或降低中枢神经系统敏感性。因此， Td可能对药代动力学和药效学耐受性均有影响 在慢性酗酒者中观察到的酒精。初步调查结果表明 类似的现象也可能发生在硫胺素缺乏的大鼠身上 在子宫里。由于需要一段时间才能发展成本病 Td在近交系中差异很大，我们评估了10个近交系大鼠 确定他们对TD的敏感性。TD敏感株(M520)和一株 选择了抗TD菌株(F344)进行进一步研究。M520大鼠 酒精代谢更快，在等量血液中受到的损害较小 酒精水平(BEC)，首选和饮用10-15倍的酒精 自由选择(乙醇溶液/水)范式优于F344大鼠。过氧化氢酶 M520大鼠的活性较高，但肝脏乙醇脱氢酶(ADH) 活动没有显著差异。TD治疗7周后，M520 大鼠的基线体温和峰值BEC的下降幅度更大 而不是同品系的对照大鼠。两个菌株都表现出双重特征 TD期间肝脏ADH升高，但过氧化氢酶无明显变化。 与同品系对照大鼠比较。

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 intraperitioneal 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 duraction of time required to develop the syndrome of TD varies greatly in outbred 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 greater 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 strain.