U. Of Colorado Professor Seeking Clues To Addiction

University of Colorado at Boulder Professor Allan Collins has received a prestigious MERIT Award from the National Institutes of Health to continue his research analyzing genetic links between alcohol and nicotine addiction.

One of only three MERIT Award winners in the nation selected by National Institute on Alcohol Abuse and Alcoholism this year, Collins will receive roughly $1 million over four years. The funding will help his research team at CU’s Institute for Behavioral Genetics pursue intriguing new lines of research they have uncovered that may lead to improved methods for drug and alcohol abuse prediction and treatment.

"I’m delighted and relieved," said Collins. "The hardest part of my job is coming up with the money each year to pay for the research done by the young people in my lab. Being a faculty member is a bit like being a parent in that we feel a sense of responsibility toward our students and researchers."

Collins, who has been on the CU faculty for 27 years, said no single landmark finding or magic bullet will mitigate the devastating biochemistry of alcohol addiction. "But I’m much more optimistic about the possibilities for diagnosis and treatment than I was 15 years ago," he said. Although Collins began his career using genetics as a tool to track the biochemical workings of alcohol, he switched to probing the biochemistry and genetics of nicotine addiction after several years, suspecting a link between the two. "It is no coincidence that 90 percent of alcoholics are smokers," he said.

In 1983, Collins’ group was the first in the world to show that chronic nicotine use in lab mice increased the number of nicotine receptors in their brains. Nearly a decade later, his group discovered that some of the receptors in the brains of mice became deactivated and desensitized to nicotine over time. "I call findings like these bricks in the wall of knowledge" said Collins. "Taken together with other findings, they can help us build a model of what type of genetic and biochemical processes in the human brain influence addiction."

Recent experiments in Collins’ lab indicate there is some overlap in genes that regulate sensitivity to alcohol and genes controlling sensitivity to nicotine. In a nutshell, mice subjected to chronic nicotine treatment show a reduced sensitivity to alcohol. "This suggests both alcohol and nicotine have common mechanisms in the nervous system," Collins said.

In one series of tests, three strains of mice that exhibited markedly different responses to alcohol were offered alcohol mixed with nicotine. Interestingly, the mice that preferred "moderate" amounts of alcohol increased their consumption of nicotine-laced alcohol considerably, while the "teetotaling" and alcoholic strains of mice showed no discernable difference in preference.

Since mice and humans have similar genes linked with biochemical responses to alcohol and nicotine, such studies may indicate that adolescents who begin smoking at an early age may be at a higher risk for alcoholism.

"By the time these kids take their first drink, they may well be less sensitive to alcohol," he said. "And people who are less sensitive to alcohol have a significantly greater chance of becoming alcoholic."

Recent work in Collins’ lab led by Research Associate Ying Lu showed that nicotine releases an inhibitory brain neurotransmitter known as GABA that dulls neuronal circuits related to anxiety, said Collins. Scientists already knew alcohol enhanced the release of GABA neurotransmitters.

But surprisingly, the CU-Boulder team showed the chronic use of nicotine in mice decreased the release of GABA, as did the chronic use of alcohol. "This shows us that two different drugs working at different places both have the same effect on the system," he said.

Collins said the experiments are interesting leads to a complex problem. "They may offer us another target, a system in the brain that could be manipulated to alter the course of alcoholism or enhance alcohol therapy."

The MERIT award will allow Collins and his team to undertake follow-up studies on the findings, he said. "It’s risky research, and it might take two or three years to chase down the answers. But the MERIT Award will allow us to follow what we think are promising leads that could result in new breakthroughs."