Liljequist S, Ahlenius S, Engel J
Naunyn Schmiedebergs Arch Pharmacol. 1977 Nov;300(3):205-16. doi: 10.1007/BF00500962.
Rats weaned at 16 days of age were treated with various ethanol concentrations (8--24% w/v) for 270 days. The effect of the chronic ethanol treatment on the growth rate, the diurnal pattern of drinking, the open field activity, and the conditioned avoidance acquisition and retention of the rats were studied. Termination of the chronic ethanol administration caused two types of withdrawal syndromes. The first, an acute withdrawal syndrome was observed within 12 h after the discontinuation of the ethanol treatment and was characterized by extreme hyperexcitability. The second, a delayed withdrawal syndrome was characterized by a more coordinated behavioural stimulation and developed first after about 3 days after the discontinuation of the ethanol treatment. Biochemically, the latter withdrawal syndrome was accompanied by an increased rate of tyrosine hydroxylation (measured as the accumulation of dopa after inhibition of aromatic amino acid decarboxylase) in the striatum and dopamine-rich limbic structures. No differences in the accumulation of 5-hydroxytryptophan were observed. Furthermore, there was an increased level of dopamine concomitant with a decreased level of noradrenaline in the limbic areas during ongoing ethanol treatment. On the 4th day after withdrawal of ethanol the endogenous levels of dopamine and noradrenaline were statistically significantly reduced in the limbic structures. The data of the present study indicate that chronic ethanol administration induces various kinds of behavioural changes and that these changes at least partially are mediated via central catecholamine mechanisms.
对16日龄断乳的大鼠用不同乙醇浓度(8%-24%w/v)处理270天。研究了慢性乙醇处理对大鼠生长速率、昼夜饮水模式、旷场活动以及条件性回避反应的获得和保持的影响。慢性乙醇给药的终止导致了两种类型的戒断综合征。第一种,急性戒断综合征在乙醇处理停止后12小时内观察到,其特征为极度兴奋。第二种,延迟性戒断综合征的特征为行为刺激更协调,在乙醇处理停止约3天后首次出现。生化方面,后一种戒断综合征伴有纹状体和富含多巴胺的边缘结构中酪氨酸羟化速率增加(以抑制芳香族氨基酸脱羧酶后多巴的积累来衡量)。未观察到5-羟色氨酸积累的差异。此外,在持续乙醇处理期间,边缘区域多巴胺水平升高,去甲肾上腺素水平降低。在乙醇戒断后第4天,边缘结构中多巴胺和去甲肾上腺素的内源性水平在统计学上显著降低。本研究数据表明,慢性乙醇给药诱导了各种行为变化,并且这些变化至少部分是通过中枢儿茶酚胺机制介导的。