NIDA Researchers Develop New Genetic Strain of Mice To Study Nicotine Addiction
A team of investigators supported by the National Institute on
Drug Abuse (NIDA), National Institutes of Health, has created a
strain of mice scientists can use to study nicotine addiction and
its associated behaviors. This research, led by Dr. Henry Lester
of the California Institute of Technology, and his colleagues at
the Institute of Behavioral Genetics at the University of Colorado,
is published in the November 5, 2004 issue of the journal Science.
"Nicotine addiction is the largest cause of preventable mortality
in the world, leading to more than 4 million smoking-related deaths
annually," says NIDA Director Dr. Nora D. Volkow. "Recent
findings also have shown that the act of smoking cigarettes can
affect biochemical systems within multiple organs that are far removed
from the lungs and upper airways. While we have a number of treatments
that have proven effective for many people, clinicians do need more
This new strain of mice, created through a process in which the
researchers altered only one amino acid through what they call "knock-in"
technology, is exceptionally sensitive to nicotine. The scientists
have shown that these mice display addiction-related behaviors,
including reward, tolerance, and sensitization to the drug. Furthermore,
they report, these actions are powerful and occur at remarkably
low nicotine doses.
"Previous work in this area of nicotine addiction has focused
on creating 'knock-out' mice, in which specific genes are removed
from the animals, which then produce less dopamine in response to
stimulation," says Dr. Lester. "But we thought that instead
of eliminating the response to nicotine, we would accentuate it
by making a hypersensitive nicotinic acetylcholine receptor that
would emphasize the pleasure pathway and allow us to study behaviors
that play roles in nicotine abuse and addiction. Thus, we developed
a 'knock-in' mouse."
Nicotine bears a molecular resemblance to the nerve chemical acetylcholine
and this allows it to bind to receptors on nerve cells called the
nicotinic acetylcholine receptors. The act of binding causes the
cells on which the receptors reside to release dopamine, a chemical
involved in the brain's pleasure/reward system.
"Studies like this are not only helping us to unravel the complexities
of nicotine addiction, but they are providing innovative ideas and
technologies that can be applied to other areas of drug abuse and
addiction," says Dr. Volkow. "But, as with other drugs,
our best treatment is prevention. We need to strengthen our programs
designed to keep people from beginning to smoke."
The National Institute on Drug Abuse is a component of the National
Institutes of Health, U.S. Department of Health and Human Services.
NIDA supports more than 85 percent of the world's research on the
health aspects of drug abuse and addiction. The Institute carries
out a large variety of programs to ensure the rapid dissemination
of research information and its implementation in policy and practice.
Fact sheets on the health effects of drugs of abuse and information
on NIDA research and other activities can be found on the NIDA home
page at http://www.drugabuse.gov.