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Drosophila as a model for drug addiction,
Ulrike Heberlein Department of Anatomy,
University of California at San Francisco.
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Drug addiction and drug abuse are major
problems in medicine and society.
The Center for Disease Control recently
reported that in the year 2000, over half
a million people died in the United States
as a consequence of excessive drug use.
Despite the immensity of the problem,
few treatment strategies
are currently available and those that
exist have met with limited success.
The reasons for this are multi-faceted.
First, drug addiction is still not
broadly acknowledged as a disease and
the associated stigma has
hampered human studies.
Second, while it is well
established that genetic and
environmental factors contribute to an
increased risk for addiction, the genetic
factors are quite complex and have so
far eluded definitive identification.
Finally, while the primary sites of
action of many abuse drugs are known,
little is known about the cellular and
molecular mechanisms by which drug use
changes the brain into the addicted state.
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Drosophila was introduced in the mid
1990s as a model system to help define
the mechanisms by which abuse drugs act in
the nervous system to alter behavior and
the mechanisms by which the brain
changes upon repeated drug exposure.
The approach relied on 2 main assumptions.
1st, that the mechanisms by which genes
regulate drug induced behaviors would be
conserved in evolution.
In that lessons learned in flies would
therefore be applicable to mammals,
including humans and 2nd that by studying
some relatively simple behaviors such as
acute drug responses,
something would be learned about the much
more complex process of addiction.
Flies provide of course, economy of scale,
the benefit of about 100 years
of classical genetics and several
decades of molecular genetic analysis.
They have a sequence genome and
have shown a substantial degree of
functional conservation with mammals.
Place had a complex nervous system in are
capable of many sophisticated behaviors.
They have been and continue to be
an extremely successful model system in
behavioral genetics where they have helped
decipher the basis of circadian rhythms,
learning and memory, and
courtship, among others.
