Background: 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.
Conclusions: 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.