Research Profile - Of mice and addiction
A McGill researcher is mapping the genes that play a role in alcoholism and drug use to draw a clearer picture of addiction
At a Glance
Who - Dr. Kathryn Gill, Director of Research at the Addictions Unit of the McGill University Health Centre.
Issue - Understanding how genes influence the development of addiction is a major challenge in mental health research.
Approach - Researchers can use rodent models to map and isolate genes that are involved in the regulation of sensitivity to cocaine, nicotine and alcohol.
Impact - Indentifying genetic factors related to drug and alcohol sensitivity and consumption will eventually lead to the design of new treatments.
Some mice get a kick from cocaine. Others, not so much.
"I have one strain called the C57 Black Six which is a 'druggy' mouse," says McGill University's Dr. Kathryn Gill. "It loves cocaine. It drinks more alcohol than water if you give it a choice. And it self-administers nicotine as well as cocaine. Then I have another strain, the AJ, which I call the teetotaler mouse; it doesn't like cocaine much."
The tiny creatures are part of a big story. Tracking their genetic differences could help explain why some people are at a higher risk than others for alcoholism and drug addiction.
"These two strains of mice are genetically very different," says the Dr. Gill, whose work is funded by the Canadian Institutes of Health Research. "So that tells us right away that there are genes involved because both mice are in the same environment."
Dr. Gill is mapping the chromosomal landscape where the response to addictive substances occurs. By using crossbred strains of the mice – mixing the genomes of the druggy C57s with the temperate AJs – Dr Gill hopes to pinpoint the genes that play a role in the sensitivity to addiction.
"Working with rodent models, we can actually knock out a gene and see what happens to the level of drug use. If you take a gene out, does the behaviour change? Do they still consume as much?"
Dr. Gill has identified "a very positive gene candidate" she believes plays a role in cocaine addiction. She's testing to see if the mice still like the drug when the gene is removed.
"I'm very interested to find if it's specific to cocaine. I work at the Addictions Unit of the McGill University Health Centre and our patients often come to us consuming more than just one drug. There may be some genes that are drug specific, but it's also possible that there is a collection of genes that are not drug specific that increase the likelihood of addiction."
The idea that addiction has a genetic component is not new: it has long been known that alcoholism runs in families. When put up for adoption, the children of alcoholic parents have a three times higher rate of alcoholism – even if their adoptive parents are non-drinkers, says Dr. Gill.
But genes only tell part of the story.
"While there is a genetic vulnerability to addiction that's passed from generation to generation, the environmental impact is also very strong," explains Dr. Gill. "We have to think multi-dimensionally all the time. We cannot be thinking about just the genes or just the environment. "
Along with understanding the impact of environmental factors, mapping uncharted genetic territory is a key step in getting a clear picture of addiction, says Dr. Gill.
"Until we've mapped these genes we won't be sure what their biological function is and how they affect behaviour. How is it that some genes – whether they are turned on or off – influence the likelihood that someone becomes addicted? We're very far from answering that question. But we're working towards it."
The Study
By using rodent models to study sensitivity to addiction, Dr. Gill is "emphasizing the biological" by taking all environmental influences out of the equation.
"We're just looking at the potential genetic-based differences between rodents in terms of their reaction to drugs," she explains. "The idea is to create a model where you can isolate genes that influence drug consumption and see what they do."
The mice are given cocaine, alcohol, nicotine and opiates, either through feeding tubes or intravenously. They can self-administer the drugs by pressing a lever.
"It's really quite interesting. They show really high self-administration of the drugs that humans also tend to like."
"It's important to understand that genes are not deterministic. They form part of the fabric, the background of all of our functioning. Everything from Day 1 onward – including the intrauterine environment, nutrition and our socialization – is going to influence how we turn out as human beings."
-- Dr. Kathryn Gill