Exploring the Neurobiology of Ethanol Relapse and Its Prevention Using N-Acetylcysteine

The alcohol use disorder (AUD) is a complex, chronic pathology with a high relapse rate. Resumption to alcohol intake after a long period of abstinence is one of the most severe handicaps of this pathological condition. Consequently, in the last decade, a wealth of studies has focused on the neurobiological mechanisms involved in various phases of AUD, including relapse to alcohol consumption. To study the mechanism underlying the neurobiology of relapse, several preclinical models have been proposed and tested. In this chapter, we describe first these models and analyze their advantages and drawbacks. Second, we target our attention in a model with high translational power based on the alcohol deprivation effect (ADE). This is, probably, the most commonly used preclinical approach to study the ethanol relapse-like drinking behavior due to its face, predictive, and ecological validity. We will describe our recent reported results, which allowed to identify two subpopulations of animals according to the alcohol relapse-like drinking behavior displayed. The different neurobiological alterations observed between both subpopulations will be also presented. They may be probably involved in the relapse neurobiology. Finally, we will describe experimental data obtained using the ADE model. These results show that N-Acetylcysteine (NAC), an antioxidant drug with glutamatergic and antiinflammatory capabilities, is able to prevent ethanol relapse.