Centre de Neurosciences Cognitives et Comportementales, Université de Liège, Boulevard du Rectorat 5/B32, Liège, Belgium.
Psychopharmacology (Berl). 2012 Feb;219(4):1165-77. doi: 10.1007/s00213-011-2453-7. Epub 2011 Sep 1.
The maturing adolescent brain has been suggested to be more sensitive than the adult brain to ethanol-induced neuroadaptations. In animal studies, sensitization to the stimulant effects of ethanol is used to study the vulnerability to chronic ethanol-induced neurobehavioral alterations.
The aim of the present study was to systematically characterize age-dependent changes in the development and expression of the sensitization to the stimulant effects of a range of ethanol doses in female Swiss mice. Three ages were studied: 21-day-old mice (postweanlings), 35-day-old mice (adolescents), and 63-day-old mice (adults).
Postweanling, adolescent, and adult mice were daily injected with saline or various ethanol doses (1.5 to 4 g/kg) for 7 days. They were then tested for acute and sensitized locomotor activity.
Postweanling and adolescent mice were more sensitive than adult mice to the acute stimulant effects of ethanol. In adult mice, daily injections of ethanol at doses between 2.5 and 4 g/kg led to significant sensitization. Higher ethanol doses (3.5 and 4 g/kg) were required to induce sensitization in postweanling and adolescent mice. However, younger mice showed ethanol sensitization of higher magnitude.
Young mice develop very strong ethanol sensitization at doses that mimic binge drinking in humans. These results might explain why early ethanol drinking during adolescence is related to a higher prevalence of subsequent alcohol disorders.
有研究表明，青春期的大脑比成年大脑更容易受到乙醇诱导的神经适应性改变的影响。在动物研究中，通过研究对乙醇兴奋作用的敏感性，来研究对慢性乙醇诱导的神经行为改变的易感性。
本研究旨在系统地描述雌性瑞士小鼠中一系列乙醇剂量刺激作用敏感性的发育和表达随年龄的变化。研究了三个年龄组：21 天大的小鼠（新生期后）、35 天大的小鼠（青春期）和 63 天大的小鼠（成年期）。
新生期后、青春期和成年期小鼠每天接受盐水或不同剂量的乙醇（1.5 至 4 g/kg）注射 7 天。然后对它们进行急性和敏化运动活动测试。
新生期和青春期小鼠对乙醇的急性刺激作用比成年小鼠更敏感。在成年小鼠中，每天注射 2.5 至 4 g/kg 的乙醇会导致明显的敏化作用。在新生期和青春期小鼠中，需要更高剂量（3.5 和 4 g/kg）的乙醇才能诱导敏化作用。然而，年幼的小鼠表现出更高幅度的乙醇敏化作用。
年幼的小鼠在模仿人类 binge drinking 的剂量下会产生非常强烈的乙醇敏化作用。这些结果可能解释了为什么青少年时期早期饮酒会导致更高的后续酒精障碍患病率。
