Harris R A
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, 78712, USA.
Alcohol Clin Exp Res. 1999 Oct;23(10):1563-70.
This review is based on a plenary lecture presented at the 1999 meeting of the Research Society on Alcoholism. It provides an overview of the search for sites of action for ethanol in the brain. Initial studies were directed at interaction of ethanol with membrane lipids, but during the past decade, emphasis has been shifted to protein sites, particularly those on ion channels. Molecular biological techniques have provided the opportunity to study isolated channels in cellular expression systems and also provide the opportunity to manipulate these channels in mutant mice.
There is now compelling evidence that multiple ion channels are affected by ethanol and growing support for the idea that ethanol interacts directly with specific sites on ion channels. The key, and unanswered, question is which of these channels are responsible for alcohol-induced behaviors such as intoxication, tolerance, dependence, or craving. Mutant mice will likely give (some) answers to these questions during the next decade.
本综述基于在1999年酒精中毒研究学会会议上发表的全会演讲。它概述了在大脑中寻找乙醇作用位点的研究情况。最初的研究针对乙醇与膜脂的相互作用，但在过去十年中，重点已转向蛋白质位点，尤其是那些位于离子通道上的位点。分子生物学技术为在细胞表达系统中研究分离的通道提供了机会，也为在突变小鼠中操纵这些通道提供了机会。
现在有令人信服的证据表明多种离子通道受乙醇影响，并且越来越多的人支持乙醇直接与离子通道上的特定位点相互作用这一观点。关键且未得到解答的问题是这些通道中的哪些导致了诸如中毒、耐受性、依赖性或渴望等酒精诱导的行为。突变小鼠可能会在未来十年为这些问题给出（一些）答案。
