Inhibition of Protein Kinase C Epsilon as a Treatment for Alcohol Use Disorder: A Systematic Review
Abstract – Alcohol use disorder (AUD) is a global problem with a large economic and human cost, so finding effective treatments of AUD is a priority. In this systematic review, the usefulness of inhibitors of protein kinase C epsilon (PKCε) in treating AUD was assessed. Studies on PubMed were selected if they fit a set of criteria for inclusion and exclusion, including whether they were relevant to the question or whether they contained predetermined keywords. Through the analysis of 22 papers, it was found that mice with PKCε inhibited or removed displayed decreased ethanol consumption, preference, and withdrawal symptoms, but also exhibited increased sensitivity to ethanol. PKCε was identified as a component of the mGluR5 and GABAA receptor pathways, both of which are involved in regulation of alcohol addiction. Inhibition of PKCε caused shifts in these pathways that directly or indirectly led to decreases in ethanol consumption. These results indicate that PKCε plays a critical role in the regulation of alcohol addiction that may be targeted through use of inhibitors to treat AUD. Though more research is needed on PKCε inhibition’s effects in humans, this paper suggests that inhibitors of PKCε are a viable treatment for AUD and require further attention.