MOLECULAR AND CELLULAR ADAPTATIONS IN SIGNAL-TRANSDUCTION PATHWAYS FOLLOWING ETHANOL EXPOSURE

The purpose of this review is to provide an overview of the acute acti ons of ethanol on signal transduction, as well as a selective consider ation of some of the long-term adaptive changes in signal transduction pathways that may underlie clinical manifestations of ethanol depende nce, tolerance, withdrawal, and addiction. The acute intoxicating effe cts of ethanol have been widely attributed to its ability to block vol tage-gated Ca2+ and Na+ channels and N-methyl-D-aspartate glutamate re ceptor cation channels, and to facilitate GABA(A) receptor Cl- channel s. Adaptive changes in these same proteins following chronic ethanol e xposure may contribute to physical and psychological signs of ethanol dependence and withdrawal. Ethanol, as with other drugs of abuse, also acutely activates the mesolimbic dopamine pathway, an effect which li kely accounts, at least in part, for ethanol's acute reinforcing prope rties. Studies directed at unraveling the biochemical and molecular ba sis of ethanol's acute and chronic actions may lead to the development of novel pharmacotherapeutics that mitigate aspects of acute ethanol intoxication and, more importantly, treat the effects of withdrawal an d addiction (craving) associated with long-term ethanol abuse. (C) 199 5 Wiley-Liss, Inc.