Obernier Jennifer A, White Aaron M, Swartzwelder H Scott, Crews Fulton T
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, 27599-7178, USA.
Pharmacol Biochem Behav. 2002 Jun;72(3):521-32. doi: 10.1016/s0091-3057(02)00715-3.
Impairments of learning and memory are common neuropsychological sequelae of chronic alcohol abuse. Alcoholics often have impairments of anterograde memory, including spatial memory dysfunction, and a tendency toward response perseveration. This study was designed to assess the effects of binge ethanol exposure on neurodegeneration and cognitive function. Rats were given ethanol three times daily for 4 days. Silver staining revealed neurodegeneration in the olfactory bulb, piriform cortex, perirhinal cortex, entorhinal cortex, and dentate gyrus. After withdrawal, behavioral testing in the Morris water maze revealed significant differences in reversal learning between treatment groups. Ethanol-treated animals required more trials to learn the reversal task, entered the previously trained quadrant more often, and spent more time there than controls. [3H]PK-11195 binding, an index of CNS damage, was elevated in the piriform cortex of ethanol-treated animals. Thus, binge ethanol exposure resulted in neurodegeneration of a corticolimbic circuit with common excitatory inputs from the olfactory bulb and was associated with perseverative responding on a spatial learning task. These studies suggest that a single binge drinking episode could cause neurodegeneration and cognitive dysfunction in humans. The perseverative nature of the behavioral deficit could be related to both cognitive dysfunction and the behavioral components of the addiction process.
学习和记忆障碍是慢性酒精滥用常见的神经心理学后遗症。酗酒者通常存在顺行性记忆障碍，包括空间记忆功能障碍，以及反应持续倾向。本研究旨在评估暴饮乙醇对神经退行性变和认知功能的影响。大鼠每天给予乙醇3次，共4天。银染显示嗅球、梨状皮质、嗅周皮质、内嗅皮质和齿状回存在神经退行性变。撤药后，在莫里斯水迷宫中的行为测试显示治疗组之间在逆向学习方面存在显著差异。乙醇处理的动物学习逆向任务需要更多的试验次数，比对照组更频繁地进入先前训练的象限，并且在那里花费更多时间。作为中枢神经系统损伤指标的[3H]PK-11195结合在乙醇处理动物的梨状皮质中升高。因此，暴饮乙醇导致了一个具有来自嗅球的共同兴奋性输入的皮质边缘回路的神经退行性变，并与空间学习任务中的持续反应相关。这些研究表明，单次暴饮可能会导致人类神经退行性变和认知功能障碍。行为缺陷的持续性质可能与认知功能障碍以及成瘾过程的行为成分都有关。
