Vertebrate endogenous opioid neuropeptides are released by post-translational proteolytic cleavage of precursor proteins. Proenkephalin-A is one of the three opioid neuropeptide precursor molecules of the opioid pentapeptides Met- and Leu-enkephalin, which compete with and mimic the effects of opiate drugs. Upon cleavage, each proenkephalin peptide results in the generation of four copies of Met-enkephalin, two extended copies of Met-enkephalin, and one copy of Leu-enkephalin. Proenkephalin opioid neuropeptide is one of the key neurobiological substrates of addiction disorders implicated in reward, mood regulation, stress response, and motor function.