Emerging neurochemical concepts in the actions of ethanol at ligand-gated ion channels

Both data and opinion are beginning to unify a consensus concerning the neurochemical mediation of the effects of ethanol in the CNS. This review of the literature is offered as an introduction to the molecular and cellular aspects of the neurochemical effects of ethanol for behavioral pharmacologists. As such, this review emphasizes the receptor pharmacology of ethanol over its behavioral effects. The unifying principle throughout the review is that ethanol has selective effects at particular ionotropic receptors, including GABA(A), NMDA and 5-HT₃ receptors. Current concepts of how ethanol may selectively interact with these receptor systems are discussed. In particular, the molecular characterizations of these receptors are reviewed to provide a foundation for understanding the differential interaction of ethanol with particular receptor subtypes and integrating data addressing the behavioral actions of ethanol. Extension of the neurochemical effects to behavioral outcomes is explored primarily via drug discrimination procedures. The recent advances that are highlighted include the receptor basis for regional sensitivity to ethanol and potential interactions of ethanol-induced neurochemical activity associated with alcohol intoxication. The integration and understanding of how multiple receptor systems interact to influence a behavioral outcome will remain an important challenge for behavioral pharmacologists interested in the effects of ethanol.