of Virginia Researchers Link Cocaine Addiction Responses To Biological
11, 1999 -- A new University of Virginia study indicates
that cocaine sensitization -- which is linked to addiction -- might
be associated with circadian genes, the genes that set the biological
clock. An implication of the finding is that cocaine addiction could
be viewed and treated as a disease rather than as a criminal behavior
problem. The study appeared in the Aug. 13, 1999 issue of the journal
exciting new research has given us a clue to the specific genetic
mechanisms that influence vulnerability to addiction," says Alan
I. Leshner, director of the National Institute on Drug Abuse, which
funded the study with the National Institute of General Medical
Sciences. "Once it is clear, these mechanisms could become the basis
for predicting who is most at risk for addiction and thus become
a major aid in preventing this national health problem."
enabling the potential development of drugs to treat cocaine addiction,
this research holds out the prospect that so-called "clock" genes
-- which are involved in setting and maintaining the body's internal
clock -- might have other, as yet undiscovered, roles in the body
and brain. These studies also hold hope for discovering common biological
abnormalities underlying sleep/wake disturbances and mood disorders.
study opens up the field of drug studies to thinking how a totally
unexpected set of genes functions in response to drugs," says Jay
Hirsh, professor of biology
at U.Va. and senior author of the report. For several years he has
been seeking to understand the genetics of behavioral responses
and his team, which includes doctoral student Rozi Andretic and
technician Sarah Chaney, use fruit flies as their genetic models
for humans. Fruit flies and humans have many genetic similarities;
therefore the flies can be used as a tool to study the complex biological
processes underlying drug abuse. Genetics researchers have long
been able to manipulate genes in fruit flies for investigations
of nervous system pathways.
flies used by Hirsh's team were mutated to lack certain circadian
genes. These insects did not become sensitized to cocaine, a process
in which repeated doses of the drug produce increasingly severe
responses. Flies containing functional circadian genes did become
sensitized to cocaine. This indicates that certain circadian genes
not only play a critical role in regulating the biological clock,
but they may also function in ways that allow susceptibility to
this study, cocaine was administered as an aerosol, and the insects'
responses were closely monitored and videotaped for comparison.
"We may come to see drug addicts more in terms of their genes, than
as people who are not in control of their behavior. Apparently genes
may be determining behavior in the case of drug abuse."
the past several years, Hirsh has used the fruit fly to probe some
of the brain's molecular mysteries, such as the circuitry involved
in learning, memory, and muscle movement. While researching core
communications pathways in the nervous systems of fruit flies, Hirsh
and his colleagues reasoned that by testing the effects of cocaine
on fruit flies, they might be able to better understand the molecular
underpinnings of cocaine-induced behavior and addiction.
year, the team initially showed that normal fruit flies respond
to crack cocaine in manners strikingly similar to vertebrates, developing
sensitized responses to repeated doses of cocaine. The work laid
the foundation for the current studies elaborating the possible
molecular bases for cocaine addiction in people, including other
recently published findings in the current online issue of Current
that implicate tyramine, one of the body's naturally occurring molecules,
as the likely perpetrator of cocaine sensitization in fruit flies.
Fariss Samarrai, (804) 924-3778.