title: Molecular and cellular adaptations in signal transduction pathways following ethanol exposure.
abstract: The purpose of this review is to provide an overview of the acute actions of ethanol on signal transduction, as well as a selective consideration of some of the long-term adaptive changes in signal transduction pathways that may underlie clinical manifestations of ethanol dependence, tolerance, withdrawal, and addiction. The acute intoxicating effects of ethanol have been widely attributed to its ability to block voltage-gated Ca2+ and Na+ channels and N-methyl-D-aspartate glutamate receptor cation channels, and to facilitate GABAA receptor Cl- channels. Adaptive changes in these same proteins following chronic ethanol exposure 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 likely accounts, at least in part, for ethanol's acute reinforcing properties. Studies directed at unraveling the biochemical and molecular basis 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 and addiction (craving) associated with long-term ethanol abuse.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: L W
authors.initials: LW
authors.lastname: Fitzgerald
authors.forename: E J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000437:Alcoholism / Q000503:physiopathology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000431:Ethanol