in animals, whereas decreased CREB function had the opposite effect.35, 36, 39 Although no change in opioid-binding sites or morphine-induced analgesia was observed in CREBαδ-deficient mice,40 alterations in dose-dependent morphine-induced reward were also reported in CREBαδ-deficient mice.41 Altogether, these reports indicate the involvement of CREB and the cAMP pathway in the analgesic and rewarding effects of opioids. Higher mRNA expression levels of the CREB1 gene in subjects with the C/C genotype in the rs2952768 SNP identified in our GWAS may indicate elevated CREB function and decreased sensitivity to the rewarding effects of opioids, resulting in greater postoperative opioid analgesic requirements and less vulnerability to dependence on other drugs.
