Addiction to drugs is a chronic complex relapsing brain disease that causes major medical, social and economic problems and is caused by genetic, epigenetic, environmental, and drug-induced factors. The endogenous opioid system plays a key role in drug addiction, and mediates the analgesic and rewarding properties of drugs. The endogenous opioid family is a network of genes coding for neuropeptide ligands and their cell surface receptors. This system consists of four major subtypes of 7-transmembrane, G protein-coupled opioid receptors: mu, kappa, delta and receptor-like, encoded by distinct genes (OPRM1, OPRK1, OPRD1, and OPRL1), which are stimulated by endogenous opioid peptides: beta-endorphin, prodynorphin, enkephalin, and orphanin/nociceptin, encoded by POMC, PDYN, PENK, and PNOC, respectively, as well as exogenous opiates. The receptors' genes are highly conserved in their 7-transmembrane domain, but not in their amino and carboxyl termini, reflecting on their different ligand binding ability and signal transduction pathways (for figures see LaForge et al. 2000). The ligands' genes all share overall similar structure with a single intron in the coding region. The opioid system is presumed to have been formed by
