NIH funds $1.5 million study of transgenerational threat from amphetamines

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School of Medicine & Health Sciences


GRAND FORKS, N.D.—If your mother or father were addicted to amphetamines, does that increase your risk of becoming addicted? An answer to that question is a focus of a $1.5 million, five-year grant to the University of North Dakota School of Medicine and Health Sciences from the National Institutes of Health’s National Institute on Drug Abuse. The study, titled “Amphetamine Causes Transgenerational Effects,” will be led by Associate Professor Lucia Carvelli, PhD , in the Department of Biomedical Sciences.

“Although addictions show no clear pattern of inheritance, family history represents one of the greatest risk factors for drug addiction,” Carvelli said. “Numerous family, adoption, and twin studies have shown that an individual’s risk to develop addiction tends to be proportional to the degree of genetic relationship to an addicted relative. In other words, parents with a history of addiction are more likely to have kids that will develop an addiction as well.”

Although social studies support that addiction can be inherited, no one knows what the mechanisms are that cause this inheritance.

“A common characteristic among all addictive drugs is that they directly or indirectly increase the activity of dopamine in the brain,” Carvelli said. “Dopamine is one of the main chemicals promoting neural signaling in those areas of the brain that are responsible for the reward system. In animals, including humans, the reward system is activated every time we perform an action that is important for our own survival, such as eating or sex.”

However, Carvelli said that amphetamines and other drugs of abuse “hijack the function of dopamine in the reward system and promote positive-reinforcing behaviors directed toward the intake of the drugs. The pleasure we experience when we eat our favorite dish is replaced by a much stronger pleasure produced by the drugs.”

For years, Carvelli has studied how amphetamines affect specific proteins of the reward system. Her research relies on the study of a tiny creature with a long scientific name: Caenorhabditis elegans or C. elegans.

C. elegans is a nematode, a transparent soil-dwelling roundworm that is about 1 millimeter in length, the width of the sharpened tip on a No. 2 yellow pencil. Most importantly, it shares a common ancestor with humans, which means that many of the same genes that guide development and disease in C. elegans are the same as those found in humans.

Scientists take advantage of the worm’s relatively simple genome (its genetic material), its short life span, the ease of manipulating its genetics, and the complete map of what genes affect the fate of every cell. C. elegans is a model research organism whose use has led scientists to significant discoveries about human cancer, kidney disease, neurodegenerative diseases like Alzheimer’s, and neurodevelopmental disabilities as well as how aging affects these processes.

“In our preliminary work, we found that in C. elegans chronic amphetamine treatment during development generated adults that are hypersensitive to amphetamine,” Carvelli said. “Remarkably, we found that this hypersensitivity to amphetamine was inherited in progeny. This result represents the first evidence supporting the hypothesis that drugs of abuse such as amphetamine can induce transgenerational effects. That is, chronic use of amphetamine during development induces physiological changes that persist during the adult stage of an individual and can be passed down to future generations.”

This discovery raised a lot of interest at the National Institute on Drug Abuse. When Carvelli applied for funding from the NIDA, the NIH institute approved her current project after the first grant submission. Only a small percentage of researchers are funded by the NIH after their first grant application.

“The long-term goal of this grant is to investigate the potential role that regulation of gene expression plays in mediating drug-induced behaviors and the inherited predisposition to addiction,” Carvelli said. “Thus our data collected on amphetamines might be useful to understand how other drugs of abuse, such as cocaine and alcohol, generate their long-term effects.”

Carvelli noted that the mechanisms that control gene expression are reversible and can be modified by drugs that are commercially available. “Our project also includes a set of experiments designed to test whether pharmacological intervention prevents the long-term and transgenerational effects caused by chronic use of amphetamine during development.”