Stress responsivity, addiction, and a functional variant of the human mu-opioid receptor gene.
Discovery and characterization of the functional A118G mu-(mu)-opioid receptor variant led to hypotheses, now in part proven, about its role in alterations of endogenous human physiology and in responses to opioid antagonist administration. Differences in cellular expression levels, ligand binding, and signal transduction for variant receptors have been documented in vitro. Human genetic studies also indicate that individuals carrying one or two copies of the 118G allele may have increased risk for opiate and alcohol addictions and that this polymorphism may also explain some of the variability in success of opioid antagonist treatment for alcoholism. Future research will further define the role of the A118G variant in addictive diseases and their treatment, in pain perception and opioid analgesia, and for a myriad of other responses mediated by the mu-opioid receptor.
Kreek
Mary Jeanne
MJ
Laboratory of the Biology of Addictive Disease, The Rockefeller University, New York, NY 10021, USA. kreek@rockefeller.edu
LaForge
K Steven
KS
D006801:Humans; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological; D019966:Substance-Related Disorders / Q000378:metabolism*
D017450:Receptors, Opioid, mu