Ciccia R M, Langlais P J
Department of Psychology, San Diego State University, California 92120, USA.
Alcohol Clin Exp Res. 2000 May;24(5):622-34.
The prolonged and heavy consumption of ethanol has been associated with thiamine deficiency and a wide range of cognitive and memory impairments. The present study was undertaken to test the hypothesis that ethanol and thiamine deficiency act synergistically, producing more severe clinical neurological disturbances and cognitive and memory impairments than either thiamine deficiency or chronic ethanol alone.
The acute neurological and long-term behavioral consequences of combined chronic (32 weeks) ethanol consumption (20% v/v in drinking water) and three separate 4-week long episodes of dietary thiamine deficiency (ET/TD) versus ethanol (ET) or thiamine deficiency (TD) treatments alone were examined in male Sprague Dawley rats aged 12 weeks at the start of treatment.
The ET/TD group lost less weight than the TD group during each episode of thiamine deficiency. Contrary to expectations, the progression and severity of ataxia, impaired righting reflexes, and opisthotonic posturing were similar in the ET/TD and TD groups. None of the ET animals displayed any neurological or behavioral symptoms during treatment. After withdrawal from ethanol and a 7-week recovery period, none of the groups differed in spontaneous activity. On subsequent testing, the ET group displayed a significant increase in perseverative responding in a spontaneous alternation task. A small but significant proportion of ET/TD (23%), ET (17%), and TD (8%) animals were unable to reach criterion on an initial nonmatching-to-position task (NMTP) or in two subsequent reversals of the matching and NMTP tasks, which indicated persistent learning impairments. A large proportion of animals in each of the three groups demonstrated significantly reduced accuracy compared with controls at longer delays of matching-to-position tasks (MTP), but only the ET group was consistently impaired at the shorter delays. There were no significant correlations between blood ethanol concentration and any of the learning and memory measures.
These results indicate that the interaction of chronic ethanol consumption and bouts of TD is both domain specific and not always synergistic. Learning and reference memory appear to be sensitive to a synergistic interaction of ET and TD, whereas short-term working memory disturbances are most affected by ET and neurological symptoms are most associated with TD. Furthermore, neither the presence of neurological symptoms nor blood ethanol concentrations appear to be good predictors of learning and memory deficits.
长期大量摄入乙醇与硫胺素缺乏以及广泛的认知和记忆障碍有关。本研究旨在验证以下假设：乙醇和硫胺素缺乏具有协同作用，与单独的硫胺素缺乏或慢性乙醇摄入相比，会产生更严重的临床神经功能紊乱以及认知和记忆障碍。
在治疗开始时，对12周龄的雄性Sprague Dawley大鼠进行研究，考察联合慢性（32周）乙醇摄入（饮用水中体积分数为20%）与三个单独的为期4周的饮食性硫胺素缺乏期（ET/TD），以及单独的乙醇（ET）或硫胺素缺乏（TD）处理的急性神经学和长期行为后果。
在硫胺素缺乏的每个阶段，ET/TD组体重减轻程度低于TD组。与预期相反，ET/TD组和TD组共济失调、翻正反射受损及角弓反张姿势的进展和严重程度相似。在治疗期间，ET组动物均未表现出任何神经学或行为症状。戒断乙醇并经过7周恢复期后，各组的自发活动无差异。在随后的测试中，ET组在自发交替任务中的持续性反应显著增加。一小部分但比例显著的ET/TD（23%）、ET（17%）和TD（8%）动物在初始位置非匹配任务（NMTP）或随后两次匹配和NMTP任务反转中未达到标准，这表明存在持续性学习障碍。在位置匹配任务（MTP）较长延迟时，三组中每组的大部分动物与对照组相比准确性显著降低，但只有ET组在较短延迟时持续受损。血液乙醇浓度与任何学习和记忆指标之间均无显著相关性。
这些结果表明，慢性乙醇摄入与硫胺素缺乏发作之间的相互作用具有领域特异性且并非总是协同的。学习和参考记忆似乎对ET和TD的协同相互作用敏感，而短期工作记忆障碍受ET影响最大，神经学症状与TD关联最密切。此外，神经学症状的存在和血液乙醇浓度似乎都不是学习和记忆缺陷的良好预测指标。
