French T A, Clay K L, Weiner N
Department of Pharmacology, University of Colorado School of Medicine, Denver.
J Pharmacol Exp Ther. 1989 Aug;250(2):556-64.
Long-sleep (LS) and short-sleep (SS) mice, bred for differences in initial sensitivity to ethanol, were found to differ considerably in the effect of ethanol on brain tyrosine levels. Brain tyrosine levels are decreased in both lines of mice over a 120-min period after ethanol, but the onset of the decrease occurs earlier (15 min vs. 60 min) and the extent of the decrease is greater (39% vs. 18%) in LS mice. This phenomenon is apparently related to the greater central nervous system ethanol sensitivity of LS mice, inasmuch as prior administration of tyrosine will prevent the ethanol-induced decrease in brain tyrosine levels and result in a decrease in the ethanol-induced sleep times of LS mice. An earlier study suggested a relationship between decreased catecholamine turnover in certain brain regions of LS mice and their greater ethanol sensitivity. The present observation that tyrosine pretreatment prevents or attenuates these ethanol-induced decreases in catecholamine turnover, while ethanol sensitivity is reduced, provides additional support for this apparent relationship. If the mice are pretreated with agents (large neutral amino acids) that lower brain tyrosine, the ethanol sensitivity (sleep times) increases in both lines of mice. The increased sensitivity is associated with marked decreases in brain region catecholamine turnover in both the LS and SS mice. These results are consistent with a role for catecholamine neuronal systems in mediating some of the intoxicating actions of ethanol, in general, and the differences in LS/SS ethanol sensitivity in particular.
长期睡眠（LS）和短期睡眠（SS）小鼠因对乙醇的初始敏感性不同而培育，研究发现乙醇对这两种小鼠脑内酪氨酸水平的影响存在显著差异。乙醇处理后120分钟内，两种品系小鼠的脑酪氨酸水平均下降，但LS小鼠酪氨酸水平下降的起始时间更早（15分钟对60分钟），下降程度更大（39%对18%）。这种现象显然与LS小鼠更高的中枢神经系统乙醇敏感性有关，因为预先给予酪氨酸可防止乙醇诱导的脑酪氨酸水平下降，并导致LS小鼠乙醇诱导睡眠时间缩短。早期一项研究表明，LS小鼠某些脑区儿茶酚胺周转率降低与其更高的乙醇敏感性之间存在关联。目前的观察结果显示，酪氨酸预处理可预防或减轻乙醇诱导的儿茶酚胺周转率下降，同时降低乙醇敏感性，这为这种明显的关联提供了额外支持。如果用降低脑酪氨酸水平的试剂（大中性氨基酸）预处理小鼠，两种品系小鼠的乙醇敏感性（睡眠时间）都会增加。敏感性增加与LS和SS小鼠脑区儿茶酚胺周转率显著降低有关。这些结果总体上与儿茶酚胺神经元系统在介导乙醇的一些中毒作用中所起的作用一致，尤其是在LS/SS乙醇敏感性差异方面。
