Human beings have consumed alcohol for thousands of years; its use is deeply rooted in culture and religion. In developed countries, more than 50% of the adult population consumes alcohol on a regular basis with only 9% developing dependence. Thus, the study of moderate drinking may inform the general population on neural effects of non-dependent drinking, and increase understanding of initial neural changes that underlie the development of addiction.
In a study published in Biological Psychiatry, Salling et al. investigated the neurobiological changes that occur during the initial stages of alcohol addiction. A proteomic screen of mouse amygdala showed that voluntary alcohol drinking altered expression and function of critical glutamate-mediated plasticity-linked protein networks. Mechanistic follow-up studies showed that alcohol-sensitive network nodes (CaMKII and AMPA glutamate receptors) regulate the positive reinforcing properties of alcohol. Electrophysiological studies conducted in collaboration with the Kash lab also showed that moderate drinking produced changes in glutamate-mediated synaptic function. These data suggest that alcohol-induced adaptations in amygdala CaMKIIα and AMPA receptor signaling may serve as a molecular gateway from use to abuse.
Salling MC, Faccidomo SP, Li C, Psilos K, Galunas C, Spanos M, Agoglia AE, Kash TL, Hodge CW. Moderate alcohol drinking and the amygdala proteome: Identification and validation of CaMKII as a novel molecular mechanism of the positive reinforcing effects of alcohol. Biological Psychiatry 15;79(6):430-42; 2016.