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 Cocaine
addiction linked to biological clock
By
Fariss Samarrai
A
new study, led by U.Va. Biology professor Jay Hirsh, 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 issue of the journal
Science.
"This
exciting new research has given us a clue to the specific genetic
mechanisms that influence vulnerability to addiction," said
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."
Besides
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.
"This
study opens up the field of drug studies to thinking how a totally
unexpected set of genes functions in response to drugs," Hirsh
said. For several years he has been seeking to understand the genetics
of behavioral responses to cocaine.
 Hirsh
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.
The
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
drug addiction.
For
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," Hirsh
said.
He
published related findings in the current online issue of Current
Biology, that implicate tyramine, one of the body's naturally
occurring molecules, as the likely perpetrator of cocaine sensitization
in fruit flies.
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