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National Institute on Drug Abuse -  NIDA NOTES
Volume 13, Number 6 (March, 1999)

New NIDA Initiative Focuses On Vulnerability to Drug Addiction

By Steven Stocker, NIDA NOTES Contributing Writer

Just as diseases such as asthma and diabetes tend to run in families, so does a predisposition to drug addiction, scientists are finding. This suggests that certain genes may confer a vulnerability to drug abuse and addiction. However, studies indicate that this vulnerability involves many genes and that environmental factors, such as family and community, also play a major role in shaping a person's behavior toward drugs.

To stimulate further research on the interaction between genetic and environmental factors that influence drug abuse and addiction, NIDA has launched the Vulnerability to Addiction Initiative. The Initiative will encourage research to locate genes that make people more or less at risk of becoming drug addicted, to study the composition and function of these genes, and to determine how environmental factors influence their activation, or expression. The Initiative also seeks to identify genes that play a similar role in animals. By studying the function of these genes in animals, researchers will obtain important clues to how comparable genes function in humans. Animal investigations will also be useful for studying how genetic and environmental factors interact to produce vulnerability to drug addiction and for studying experimental treatment and prevention strategies and medications.

"The more we understand about why some people abuse drugs and become addicted while others do not, the better equipped we will be to develop more effective treatment and prevention interventions," says NIDA Director Dr. Alan I. Leshner. "As research progresses, we may find that different genes confer a vulnerability to drug addiction in different ways. Some genes may increase vulnerability by affecting a person's responses to drugs or the way that person metabolizes a particular drug, while other genes may increase vulnerability by promoting personality variables, such as sensation seeking, that are associated with drug abuse. We may be able to tailor interventions to an individual's genetic makeup."

NIDA announced the Vulnerability to Addiction Initiative at a symposium titled "Prospects for the Molecular Genetics of Drug Abuse" held in conjunction with the annual meeting of the American Society of Human Genetics in Denver in October, 1998. As a major component of the Initiative, the Institute has allocated $7 million over the next 2 years to expand NIDA's efforts to identify the genes that make people vulnerable to addiction. These funds augment current NIDA funding that supports genetics research in humans, such as studying the inheritance of drug abuse traits, and in animals, such as studying drug preferences in selectively bred and genetically engineered rodent strains.

In preparation for the Initiative, last year NIDA convened genetics researchers both within and outside the drug abuse field. The scientists concluded that genetic factors play as much of a role in drug abuse and drug addiction as they do in other chronic diseases. However, that role is likely to be complex, involving multiple genes and an interaction with environmental factors. To increase the likelihood of identifying these complex genetic influences, the scientists recommended that researchers use a variety of approaches for locating candidate genes, including sib-pair analysis and association studies.

Sib-pair analysis is the most commonly used approach in disorders such as drug abuse that involve more than one gene. In sib-pair analysis, researchers compare the genetic material of sibling pairs who abuse drugs with the genetic material of sibling pairs who do not abuse drugs in order to identify candidate genes that may contribute to drug abuse.

"In genetic studies such as these, scientists often identify a gene associated with a particular disease and then only later determine that gene's function," says Dr. Jonathan Pollock of NIDA's Division of Basic Research. "After locating a candidate gene, scientists clone the gene and then study it to determine how it contributes to the disorder."

Association studies involve an approach that is opposite to the approach used in sib-pair analysis. In association studies of drug abuse, researchers hypothesize from what is known about the biochemistry of addiction that a particular gene with known location and function contributes to drug abuse. The researchers then determine whether drug abusers have a different version of this gene than nondrug abusers.

As researchers funded under the Initiative work to locate candidate genes for drug abuse, they may apply to the Center for Inherited Disease Research (CIDR) at Johns Hopkins University in Baltimore for assistance in performing genetic analyses. Researchers who are approved by CIDR will be able to send blood samples to the Center for free analyses. CIDR was established in 1996 as a joint effort by eight of the National Institutes of Health, including NIDA, to provide a central location where genetic analyses could be performed more rapidly, with greater consistency, and at lower cost than if investigators were to perform their own analyses.

NIDA is encouraging researchers conducting animal studies of possible vulnerability genes to include not only those animals that have been traditionally used in drug addiction research, such as mice and rats, but also animals that rarely have been used in this field, such as fruit flies, worms, and zebrafish. These animals breed quickly and, in some cases, much is already known about their genetic makeup. This knowledge can facilitate the process of locating candidate genes involved in drug addiction.

Studying gene function in animals even as low on the evolutionary scale as the fruit fly can provide clues regarding gene function in humans, says Dr. Pollock. "Many of the genes that affect behavior in lower animals, such as the fly, subserve similar functions in higher organisms," he says.

For More Information

Information for researchers about resources for drug abuse genetics research is available on the Genetics Workgroup section of NIDA's home page on the World Wide Web at http://www.nida.nih.gov/genetics/geneticshome.html. Included is a list of grant announcements that describe research that NIDA is currently funding, a bulletin board for researchers seeking collaborators, and a list of upcoming events and meetings dealing with the genetics of addiction.

NIDA NOTES - Volume 13, Number 6

