Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. II: Studies in selectively bred rats and mice.
Relationship of brain ethanol metabolism to the hypnotic effect of ethanol. II: Studies in selectively bred rats and mice.
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DOI：
10.1111/j.1530-0277.2001.tb02306.x
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发表时间：
2001-07
期刊：
影响因子：
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通讯作者：
Sergey M. Zimatkin;Anton V. Liopo;V. Satanovskaya;Lubov R. Bardina;R. Deitrich
中科院分区：
文献类型：
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作者：
Sergey M. Zimatkin;Anton V. Liopo;V. Satanovskaya;Lubov R. Bardina;R. Deitrich
为了阐明脑乙醛在乙醇催眠作用中的作用，我们比较了基因选择的对乙醇催眠作用不同敏感性的动物大脑中乙醇氧化能力（乙醛积累速率）和过氧化氢酶和醛脱氢酶活性。方法采用高、低或对照酒精敏感大鼠（HAS、LAS和CAS）、短睡眠和长睡眠小鼠（SS和LS），以及已知品系酒精诱导睡眠平均持续时间差异的SS × LS重组近交系小鼠。我们研究了这些动物大脑匀浆中乙醇积累乙醛的速率，并将这些值与它们对乙醇的催眠敏感性联系起来。结果：与对乙醇低敏感性的LAS大鼠和SS小鼠相比，对乙醇催眠作用高敏感性的HAS大鼠和LS小鼠脑匀浆中乙醇的乙醛积累量显著增加。研究发现，在重组SS × LS小鼠品系中，乙醇诱导睡眠的持续时间与体外乙醇衍生乙醛在大脑中的积累率之间存在相关性。睡眠时间与大脑过氧化氢酶水平没有相关性。LAS、CAS和HAS大鼠、SS和LS小鼠的脑过氧化氢酶或醛脱氢酶活性、肝脏酒精或醛脱氢酶活性均无系差异。结论：在对乙醇催眠作用的初始敏感性存在遗传差异的动物中，脑乙醛积累（而非过氧化氢酶水平）与乙醇的中心效应存在相关性。
BACKGROUND To clarify the role of brain acetaldehyde in the hypnotic effect of ethanol, we compared the ethanol-oxidizing capacity (rate of acetaldehyde accumulation) and catalase and aldehyde dehydrogenase activity in the brains of animals genetically selected for different sensitivities to the hypnotic effect of ethanol. METHODS We used high, low, or control alcohol-sensitive rats (HAS, LAS, and CAS) and short- and long-sleep mice (SS and LS), as well as SS x LS recombinant inbred mice with known strain differences in mean duration of ethanol-induced sleep. We studied the rate of accumulation of acetaldehyde from ethanol in brain homogenates of these animals and correlated those values with their hypnotic sensitivity to ethanol. RESULTS Acetaldehyde accumulation from ethanol was significantly higher in the brain homogenates from HAS rats and LS mice with high sensitivity to the hypnotic effect of ethanol in vivo, compared with LAS rats and SS mice with low sensitivity to ethanol. A correlation was found between the duration of ethanol-induced sleep and the in vitro rate of accumulation of ethanol-derived acetaldehyde in the brains of recombinant SS x LS mice strains. There was no correlation of sleep time with brain catalase levels. There were no line differences in brain catalase or aldehyde dehydrogenase or in alcohol or aldehyde dehydrogenase activity in livers of LAS, CAS, and HAS rats or in SS and LS mice. CONCLUSIONS A correlation between the brain acetaldehyde accumulation, but not catalase levels, and the central effect of ethanol was demonstrated in animals genetically differing in initial sensitivity to the hypnotic effect of ethanol.