Although previous studies mainly focused on the effect of CREB on opioid dependence, for example, morphine condition place preference,13 emerging evidence has revealed the function of CREB in immune responses, including macrophage survival, regulation of T and B lymphocytes and inducing transcription of immune-related genes, for example, IL-10.14 CREB-mediated immune regulation could be via the inhibition of NF-κB activity. This evidence concerns the gene CREB1 and opiate dependence.