Chapter 9 - From Signaling Pathways to Behavior: The Light and Dark Sides of Alcohol

Abstract

Understanding the mechanism of action of drugs of abuse, including alcohol, is central for the development of treatments for addiction. Most drugs of abuse possess very specific modes of action, that is, binding to discrete receptors in certain subsets of neurons to precipitate a singular, defined effect. Alcohol, on the other hand, exerts a multitude of effects on various receptors and signaling pathways. As a result, instead of discovering a simple mode of action, exploration into alcohol’s biological influence has unveiled an intriguing dichotomy in this drug’s effects. Although some signaling pathways altered by alcohol underlie the adverse phenotypes associated with alcohol-use disorders (what we term the “dark side” of alcohol), others serve to protect and/or delay the development of alcohol-abuse disorders (what we term the “light side” of alcohol). A better understanding of these opposing forces and the implied balancing act between them is a much-needed step towards an effective treatment for alcohol-use disorders. Because alcohol’s action on signaling has recently been reviewed in detail, this review focuses on the bridge between the molecular actions of alcohol and behavior. Recently published findings on the acute and long-term molecular adaptations that occur following the exposure of awake, behaving vertebrates and invertebrates to alcohol are described. The signaling cascades described herein are activated in response to alcohol in specific brain regions, resulting in synaptic plasticity events and/or changes in transcription and translation as well as epigenetic modifications that mediate either the dark or light sides of this drug.