Ethanol, Its Active Metabolites, and Their Mechanisms of Action: Neurophysiological and Behavioral Effects

Ethanol is the psychopharmacologically active ingredient of alcoholic drinks, but in spite of decades of intense preclinical and clinical research, the lack of a precise neurobiological mechanism of action and the complexity of its central metabolism still lead to many unanswered questions. Ethanol is the paradigmatic example of a compound whose primary pharmacological effects cannot be explained as simply due to the involvement of a single receptor/neurotransmitter, a scenario further complicated by the robust evidence that two of its main metabolites, acetaldehyde and salsolinol, exert a number of effects similar to their parent compound. For some behavioral effects ethanol is observed to have a biphasic dose response curve (e.g. motor activity), but evidence indicates that the ethanol metabolites acetaldehyde and acetate are differentially involved in the ascending and descending limbs of this curve. These observations have instigated a resurgence of interest in the importance of ethanol metabolism. Recent studies of ethanol and its metabolites have contributed substantially to our understanding of the neurobiological actions of ethanol on GABAergic and glutamatergic systems, and also have highlighted the role of ethanol metabolites in modulating mesolimbic dopamine transmission.

This Research Topic will be aimed at providing an up to date characterization of the diverse effects of ethanol in different brain areas, as well as possible mechanisms of action on different intracellular systems. Furthermore, this Topic will outline some of the hypothesized actions of ethanol and/or its metabolites on the synthesis and actions of various neurotransmitters and neuromodulators, and will discuss how these actions mediate the behavioral effects of ethanol.