However, an upregulated DYN/KOR system in various key brain regions at proximal (DYN/KOR mRNA and expression) and intermediate (CREB/ΔFosB/BDNF mediated signaling) levels could contribute to altered distal events (escalated alcohol use, affective/anxiety like behaviors, sensitization following abstinence) in alcohol dependence. This evidence concerns the gene CREB1 and Anxiety.