Ethanol consumption and resistance are inversely related to neuropeptide Y levels
Ethanol consumption and resistance are inversely related to neuropeptide Y levels
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DOI：
10.1038/24614
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发表时间：
1998-11-26
期刊：
影响因子：
64.8
通讯作者：
Palmiter, RD
中科院分区：
文献类型：
--
作者：
Thiele, TE;Marsh, DJ;Palmiter, RD
对为酒精偏好而选择性饲养的大鼠进行的遗传连锁分析发现了一个包含神经肽Y(NPY)基因的染色体区域(I)。与不爱喝酒的大鼠相比，喜欢喝酒的大鼠在几个脑区的NPY水平较低(2)。因此，我们研究了由于靶向基因破坏而完全缺乏NPY的小鼠的酒精消费(3)。在此，我们报告，与野生型小鼠相比，NPY缺陷小鼠对含有6%、10%和20%(v/v)乙醇的溶液的消耗量增加。NPY基因缺陷的NICE对乙醇的镇静/催眠作用也不那么敏感，从乙醇诱导的睡眠中更快地恢复表明了这一点，尽管血浆乙醇浓度与对照组没有显著差异，相比之下，在神经元中过度表达显著NPY基因的转基因小鼠对乙醇的偏好较低，对这种药物的镇静/催眠作用比对照组更敏感。这些数据直接证明了酒精摄入量和抵抗力与大脑中NPY水平呈负相关。
Genetic linkage analysis of rats that were selectively bred for alcohol preference identified a chromosomal region that includes the neuropeptide Y (NPY) gene(I). Alcohol-preferring rats have lower levels of NPY in several brain regions compared with alcohol-non-preferring rats(2). We therefore studied alcohol consumption by mice that completely lack NPYas a result of targeted gene disruption(3). Here we report that NPY-deficient mice show increased consumption, compared with wild-type mice, of solutions containing 6%, 10% and 20% (v/v) ethanol. NPY-deficient nice are also less sensitive to the sedative/hypnotic effects of ethanol, as shown by more rapid recovery from ethanol-induced sleep, even though plasma ethanol concentrations do not differ significantly from those of controls, In contrast, transgenic mice that overexpress a marked NPY gene in neurons that usually express it have a lower preference for ethanol and are more sensitive to the sedative/hypnotic effects of this drug than controls. These data are direct evidence that alcohol consumption and resistance are inversely related to NPY levels in the brain.