Centre de Neurosciences Cognitives et Comportementales, Université de Liège, Boulevard du Rectorat 5/B32, B-4000 Liège, Belgium.
Alcohol. 2013 Jun;47(4):317-22. doi: 10.1016/j.alcohol.2013.01.006. Epub 2013 Apr 6.
The adolescent brain has been suggested to be particularly sensitive to ethanol-induced neuroadaptations, which in turn could increase the risk of youths for alcohol abuse and dependence. Sensitization to the locomotor stimulant effects of ethanol has often been used as an animal model of ethanol-induced neuroadaptations. Previously, we showed that young mice were more sensitive than adults to the locomotor sensitization induced by high ethanol doses. However, this effect could be due to age-related differences in chronic tolerance to the sedative effects of ethanol. The aim of the present study is to assess chronic tolerance to the sedative effects of ethanol in weaning 21-day-old (P21), adolescent 35-day-old (P35) and adult 63-day-old (P63) female Swiss mice. After a daily injection of saline or 4 g/kg ethanol during 6 consecutive days, all P21, P35 and P63 mice were injected with 4 g/kg ethanol and submitted to the loss of righting reflex procedure. Our results confirm that the sensitivity to the acute sedative effects of ethanol gradually increases with age. Although this schedule of ethanol injections induces significant age-related differences in ethanol sensitization, it did not reveal significant differences between P21, P35 and P63 mice in the development of a chronic ethanol tolerance to its sedative effects. The present results show that age-related differences in the development of ethanol sensitization cannot be explained by differences in chronic ethanol tolerance to its sedative effects. More broadly, they do not support the idea that ethanol-induced sensitization is a by-product of chronic ethanol tolerance.
青少年的大脑被认为对乙醇引起的神经适应性特别敏感，这反过来又会增加青少年酗酒和依赖的风险。乙醇对运动刺激作用的敏感性常被用作乙醇引起的神经适应性的动物模型。以前，我们发现年轻小鼠比成年小鼠对高剂量乙醇引起的运动敏化更为敏感。然而，这种效应可能是由于与年龄相关的对乙醇镇静作用的慢性耐受差异所致。本研究的目的是评估断奶 21 日龄（P21）、青春期 35 日龄（P35）和成年 63 日龄（P63）雌性瑞士小鼠对乙醇镇静作用的慢性耐受。在连续 6 天每天注射生理盐水或 4 g/kg 乙醇后，所有 P21、P35 和 P63 小鼠均注射 4 g/kg 乙醇，并进行翻正反射丧失程序。我们的结果证实，对乙醇急性镇静作用的敏感性随年龄逐渐增加。尽管这种乙醇注射方案引起了与年龄相关的乙醇敏化的显著差异，但它并没有显示出 P21、P35 和 P63 小鼠在慢性乙醇耐受其镇静作用方面的发展存在显著差异。本研究结果表明，乙醇敏化的发展与年龄相关的差异不能用慢性乙醇耐受其镇静作用的差异来解释。更广泛地说，它们不支持乙醇诱导的敏化是慢性乙醇耐受的副产物的观点。
