Murad C A, Begg S J, Griffiths P J, Littleton J M
Br J Exp Pathol. 1977 Dec;58(6):606-15.
Physical dependence on ethanol was induced in TO strain mice by chronic administration of ethanol by inhalation. The severity of the behavioral syndrome of withdrawal from ethanol was quantified by a subjective scoring method. During the chronic administration of ethanol, triglycerides accumulated in livers of male or female mice with a time course similar to that of the induction of physical dependence. When ethanol was withdrawn from adult or weaning dependent mice, a relationship was observed between the decline of triglyceride concentrations in liver and the duration of the ethanol withdrawal syndrome. The addition of DL-carnitine (7% w/w) to diet during the administration of ethanol markedly inhibited the accumulation of triglycerides, and significantly reduced the intensity of the ethanol withdrawal syndrome. Administration of carbon tetrachloride ((1.3 ml/kg i.p.), however, although augmenting hepatic triglyceride accumulation, had no significant effect on the withdrawal syndrome. The results are interpreted as suggesting either that ethanol-induced liver dysfunction plays a part in dependence, or, more likely, that triglyceride accumulation reflects an ethanol-induced metabolic disorder which is itself related to the induction of dependence.
通过吸入法对TO品系小鼠长期给予乙醇,使其产生对乙醇的身体依赖性。采用主观评分法对乙醇戒断行为综合征的严重程度进行量化。在长期给予乙醇期间,雄性或雌性小鼠肝脏中甘油三酯蓄积,其时间进程与身体依赖性的诱导相似。当从成年或断奶的依赖乙醇小鼠中撤去乙醇时,观察到肝脏中甘油三酯浓度的下降与乙醇戒断综合征的持续时间之间存在关联。在给予乙醇期间,在饮食中添加DL-肉碱(7% w/w)可显著抑制甘油三酯的蓄积,并显著降低乙醇戒断综合征的强度。然而,腹腔注射四氯化碳(1.3 ml/kg)虽然会增加肝脏甘油三酯的蓄积,但对戒断综合征没有显著影响。这些结果被解释为表明,要么乙醇诱导的肝功能障碍在依赖性中起作用,要么更有可能的是,甘油三酯蓄积反映了一种乙醇诱导的代谢紊乱,而这种紊乱本身与依赖性的诱导有关。