Colext/Macondo
Cantina virtual de los COLombianos en el EXTerior
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http://www.economist.com/editorial/freeforall/focus/focus_illegal_drugs_tframese
t.html
SCIENCE AND TECHNOLOGY
Flying high
COCAINE, as addicts well know, has curious effects on the body. One of them
is "reverse tolerance": rather than becoming accustomed to cocaine with
increasing exposure (as happens with, say, alcohol), the brain becomes more
sensitive. With each hit, responses, such as fidgeting, are more
exaggerated. This sensitisation is thought to be a first step in creating
an overwhelming craving for the drug that eventually leads to addiction.
In humans, studying cocaine sensitisation is tricky since most governments
have strong views on giving drugs to the uninitiated, and tend to enforce
them with lengthy prison sentences. So instead researchers have turned to
creatures such as the fruit fly, Drosophila melanogaster, to probe the
cellular basis for cocaine craving. In this week's issue of Science,
biologists Jay Hirsh, Sarah Chaney and Rozi Andretic of the University of
Virginia report that an appetite for cocaine seems to be connected to the
mechanisms which control circadian rhythm-the so-called "body clock".
Fruit flies, like humans, have an internal biological clock that governs
their activity over a 24-hour cycle. Ms Andretic recently found that the
brain makes use of a biochemical called dopamine to regulate its circadian
rhythm. Other experiments on mice and flies have shown that dopamine is
also involved in cocaine sensitisation. So the researchers put the two
together and decided to see whether disrupting the body's internal clock
might also affect cocaine craving.
When exposed to purified "freebase" cocaine, fruit flies behave
surprisingly like junkies. They twitch, gnaw and groom themselves
compulsively while wandering about in circles. As the drug dose rises, such
erratic movements become more severe until the fly is paralysed and drops
dead. Ordinarily, one cocaine hit is enough to sensitise a fly. But Dr
Hirsh's team found that mutant Drosophila lacking genes called "Clock",
"Period", "Cycle" and "Doubletime"-all of which are known to control
circadian rhythm-also lack heightened responses to cocaine even after
multiple doses. In fact, "Doubletime" mutants proved particularly resistant
to the drug, requiring substantially higher quantities before behaving
strangely.
In fruit flies, a biochemical called tyramine seems to be responsible for
such drug responses, and Dr Hirsh thinks that tyramine regulation is the
chemical link between these two very different processes. After a single
cocaine dose, the enzyme that makes tyramine becomes more active in normal
flies. In the circadian-gene mutants, however, the enzyme's activity stays
steady after a dose of the drug, so tyramine levels remain low. The absence
of the circadian genes, which seem to regulate the release of tyramine,
prevents flies from becoming more responsive to cocaine.
Whether sky-high flies can teach scientists much about human addiction
remains to be seen. Only about a fifth of the people who use cocaine
actually become addicted to it: the puzzle lies in understanding what
distinguishes the casual user from the hard-core addict. But if the
propensity to addiction is also genetically controlled in humans, it could
provide a mechanism to address the problem at the cellular level, by
regulating tyramine or its vertebrate equivalent. It might then be possible
to treat cocaine addiction as a disease rather than a criminal activity.
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