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NIDA. (2002, January 3). NewsScan for January 3, 2002 - Research News. Retrieved from

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January 03, 2002

Researchers Report First “Genome Scan” for Drug Abuse

Results of a genome-wide search, or “genome scan,” by a team of researchers led by Dr. George Uhl, from the National Institute on Drug Abuse (NIDA) in Baltimore, Maryland, provide the first evidence that specific regions of the human genome differ between abusers of illegal drugs and nonabusers. The findings of Dr. Uhl and his colleagues are an important step toward identifying genes that affect a person’s vulnerability or resistance to substance abuse, and offer hope for identifying individuals at high risk for addiction and matching abusers with the most effective treatments.

The researchers looked for differences in the frequency of 1,494 genetic variants known as SNPs (single nucleotide polymorphisms, or “snips”) between DNA samples from 667 unrelated individuals with a history of heavy drug use and 338 individuals with no significant lifetime use of any addictive substance (controls). Using the SNP markers, whose locations in the genome are known, the research team identified more than 40 regions across the genome that differ between drug abusers and controls in DNA samples from both European Americans and African Americans. Eight of these regions previously have been linked to alcohol or nicotine dependence, suggesting that genes in these regions contribute to individual vulnerability to abuse of multiple substances.

Studies have shown that genetic factors account for about half of human drug abuse vulnerability (environmental factors account for the other half), but researchers have not yet identified the individual genes that are involved. “Once you identify the genes, then you can ask, ‘What part does this specific gene play in the overall drug abuse problem?’” Dr. Uhl says. He hopes this research will provide “knowledge about this genetic half of the problem that we can use to better match the preventions and the treatments to the people who are most likely to benefit from them.”

  • WHAT IT MEANS: Scientists have known that genetic factors play a role in determining a person’s vulnerability to substance abuse. The findings of this study identify specific regions of the human genome that may be involved, narrowing the search for genes that make a person more or less susceptible to addiction. Identifying these genes will shed light on the mechanisms of addiction and may make it possible to target treatments and prevention efforts to those individuals most likely to benefit.

The study by Dr. George Uhl, Dr. Qing-Rong (Tim) Liu, Ms. Donna Walther, and Ms. Judith Hess of the NIDA Intramural Research Program, and Dr. Daniel Naiman of the Johns Hopkins University appears in the December issue of the American Journal of Human Genetics.

Newly Discovered Receptor May Be Important In the Development of Antipsychostimulant Medications

Scientists at the Oregon Health and Science University have discovered and characterized a receptor for trace amines that may be instrumental in developing new antipsychostimulant medications.

The investigators characterized a G-protein-coupled receptor called trace amine receptor (TAR) which stimulates the production of cAMP when exposed to the trace amines tyramine, tryptamine, octopamine, and para-tyramine. This latter substance is structurally and functionally related to amphetamines.

Although TAR is found in humans, the scientists used rats to demonstrate that beta-PEA for beta-phenylethylamine, a substituted amphetamine that represents a class of hallucinogens that include mescaline, MDMA (known on the street as “ecstasy”), and MDA, is the substance that most increased the receptivity of TAR. This finding suggests that the effects of amphetamines may be mediated in part by the TAR receptor.

  • WHAT IT MEANS: The results of this study indicate that the activation of TAR may be responsible for some of the psychological effects of psychostimulants; therefore, TAR may represent an important new target for the development of anti-psychostimulant medications.

A research team headed by Dr. David K. Grandy and including James R. Bunzow, and Drs. Susan Amara and Mark Sonders published the study in the December 2001 issue of Molecular Pharmacology.