November 18, 2009

Sins of the Mothers

Opiate use during adolescence has long-term consequences for a user’s offspring, says a researcher on the genetics of addiction

By Catherine O’Neill Grace

Mothers who abuse painkillers during their adolescent years may actually predispose their offspring to becoming addicted to those same drugs, according to a biomedical researcher at the Cummings School of Veterinary Medicine.

“If you took these drugs as an adolescent, and you’re thinking, hey, that’s no big deal, that’s in the past, and now I am happy and healthy and everything’s fine,” that probably is not the case, says Elizabeth Byrnes, a research assistant professor of biomedical sciences. “You actually may be transmitting a sensitivity to opiates to your offspring. And that sensitivity is one thing that will determine how likely [the offspring] are to have a problem with those drugs,” she says.

Vicodin, the most heavily prescribed drug in the United States, is one of the most widely used drugs among high school students, says Elizabeth Byrnes. Photo: iStock

The research, which could lead to a better understanding of familial patterns of drug abuse, has implications for the 1 million Americans who are addicted to opiates, which relieve pain by binding to receptors in the brain and spinal cord.

During the adolescent years, from ages 12 to 17, the rate of drug abuse in boys and girls is about the same, Byrnes says. But girls tend to use painkillers more—at a time when their reproductive systems are undergoing rapid change.

For the research, which was published in the journal Psychopharmacology, Byrnes exposed laboratory rats to opiates during puberty. The animals were weaned from the drugs and allowed to grow into adulthood drug-free. Then they were mated and gave birth.

Among the animals exposed to the drugs, “the mothers’ fertility looks OK, and the offspring seem to be normal,” Byrnes says. “But they aren’t normal.” When the offspring were given the same painkillers as their mothers had during puberty, “they were really sensitive to them,” she says. “So somehow the mother is transmitting that sensitivity from her early exposure to the drugs.”

Drugs of Choice

“Opiates are quite popular” with the adolescent crowd, Byrnes says. “Right now it’s a big problem because of OxyContin and Vicodin,” both powerful opioid painkillers. She says that Vicodin, the most heavily prescribed drug in the U.S., is one of the most widely used drugs among high school students, lagging only behind alcohol and marijuana. “So this is a timely topic,” Byrnes says.

The 2008 Monitoring the Future Report, an annual survey of behaviors and attitudes of 8th-, 10th- and 12th-graders funded by the National Institute of Drug Abuse, found that nearly 10 percent of high school seniors reported non-medical use of Vicodin in the past year, and 4.7 percent said they had abused OxyContin. Those statistics were reinforced by a more recent study, published in the August issue of the Archives of Pediatrics & Adolescent Medicine, which found that more than one in ten high school seniors has used a prescription opioid that was not authorized by a physician.

In the next phase of her research, Byrnes will investigate whether—and how—using drugs in adolescence affects fertility and maternal behavior later on, and whether a history of drug abuse in the mother increases the chances that her offspring will also abuse drugs.

Genetics vs. Nurture

“We already know that genetic information is passed down from one generation to the next,” Byrnes says. “Is it just a matter of which genes are expressed—are you more or less hard-wired—or is it something that’s happening in terms of maternal behavior, too?”

With a three-year, $866,000 grant from the National Institute of Drug Abuse, Byrnes will examine the genetic makeup of the offspring of the mothers exposed to painkillers during puberty. “We’re going to do a whole genome scan to see which genes are being activated where.”

Ultimately, Byrnes hopes her work will lead to a better understanding of generational patterns of drug abuse. “We know it runs in families, and we know that it’s not completely genetic. In humans, we know the risk factors, but we don’t really understand a lot of the neuroscience behind it. The only way you can do that is with the animal model.”

Byrnes’ research is noteworthy because it relies on female animal models. “The vast majority of work on substance abuse is done in males,” she says. “When you’re dealing with animals, especially small laboratory animals, the females are more difficult because they have these pesky hormones that nobody wants to deal with—which can mean that half of the population is left out” of studies on substance abuse.

“We’re certainly not going to get the whole dynamic picture of what causes drug abuse,” she says, “but if we can pick up one small thing and be able to say we know that this causes an increased risk [for substance abuse], we can do a lot in terms of prevention.”

This story first appeared in the Fall 2009 issue of Tufts Veterinary Medicine magazine.

Catherine O’Neill Grace can be reached at

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