Subtle Changes In Brain Receptor Gene May Have Significant Consequences For Addiction

Scientists have identified five slightly different versions of the mu opioid receptor gene that alter the activity of a molecule called beta-endorphin, a member of the endorphin family of proteins that can numb pain, create feelings of euphoria or increase energy, which opiates and other drugs of analgesia and addiction do as well. The findings, reported by researchers from The Rockefeller University, Indiana University School of Medicine and University of Cincinnati College of Medicine in the August 4 Proceeding of the National Academy of Sciences, show for the first time that these altered molecules are distributed differently among ethnic groups and have implications for normal physiology, therapeutics and vulnerability to develop or protect from diverse diseases involving mu opioid receptors, including the addictive diseases.

"These findings are potentially very important because of the high frequency of two versions, or alleles, of this gene in the general population," says co-senior author Mary Jeanne Kreek, M.D., professor and head of the Laboratory on the Biology of Addictive Diseases at Rockefeller. "We have defined alterations in the function of one allele studied for both binding and activity."

"These interesting pre-clinical findings present a very important target for additional research into what makes people vulnerable to addictive diseases," says Alan I. Leshner, Ph.D., director of the National Institute on Drug Abuse (NIDA) of the National Institutes of Health, which funded part of the study.

The scientists studied variations in the DNA sequence of the mu opioid receptor gene called single-nucleotide polymorphisms (SNPs). The double-helical structure of DNA comprises four building blocks called nucleotides, represented by the letters A, T, G and C. The nucleotides pair-A with T, G with C-to form limitless combinations along the double helix. SNPs derive from single differences in the base pairing, which may produce changes in the pro

Contact: Joseph Bonner
Rockefeller University

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