Sounds like panacea

No way out: knockout mice are< COCAINE is the single-most abused drug
in the us. Researchers from the
University of North Carolina, Chapel
Hill and the Howard Hughes Medical
Institute of the Duke University, both in
the us, have taken the first step towards,
what they claim, a therapeutic cure for
addiction of cocaine and other drugs.
Their study on a group of genetically
manipulated mice is also yielding
fresh ideas for treating disorders like
Parkinson's disease and schizophrenia.

Symptoms like addictive behaviour
essentially have to do with a brain
chemical - cloparnme. Moreover, too
much doparnme in certain parts of
the brain makes the patient schizophrenic and too little can lead to the
tremors and rigidity associated with
Parkinson's disease.

Doparnine, essentially a neurotransmitter, is released by one nerve cell to send a signal to another. It activates the
receptor site in the synapse, the joint of
the nerve cells. Normally the cell that
releases cloparnine reclaims it within a
fraction of a second and the signal shuts
off. The reclaiming is triggered off by a
certain class of protein called the
cloparnine transporter, a molecule in the
synapse which helps the dopamine back
into the cell it was released from.

The researchers tinkered with this
faculty of the nerve cells in the mice.
They knocked out the gene responsible
for activating the doparnine transporter
in the mice and the creatures, aptly,
were dubbed as 'knockouts'. Once
doparnine was released in the brains of
the knockouts, the signal persisred for
more than 100 seconds, an unusually
long time by neurosignal transmission
time standards.

The lasting signal, transmitted and
amplified by a million synapses ends up
making the mouse very 'hyper'- The
animals run around for hours together,
fad to eat enough to maintain i7healthy
physique and often drop dead from
exhaustion. Researchers specialising in
psych4harmacology (like Marc Caron
from Duke University) immediately
rec6gnised that the frenetic state was
comparable to a person high on cocaine
and amphetamines.

Action of cocaine is to block the
dopatmirle transmitter and the resulting
long-lasting euphoria is a fallout of the
excess buildup of dopamine and not a
direct effect of the drug. With period
intakes of cocaine the nervous system
also gets used to periodic buildups of
doparnine and this is the first step
towards having an addiction The
theory was confirmed by the fact that
the mice had no effect whatsoever of
cocaine, however high the dosage might
be. With no doparturre transporter in
them, the drug had no target to work on
and no means of raising the cloparnme
level in the synapses.

A promising denouement of the
study is the fact that the mice were not
affected by amphetamine too.
Amphetamine, another widely used
drug, is also known to have similar
psychosomatic effects. Alan Leshner,
director of the National Institute
on Drug Abuse, was understandably
excited by the results - hailing it as "a
major advance" in the study of addictions. "The biggest single need in this
country.(us) ts for a cocaine medication,
we have nothing other than behavioural
treatments", Leshncr said. Findings
of the study support the idea that
the drugs that block cocaine at the
transpoLter without affecting dopamine
levels could reduce addicts' cravings for
the dope.

,The study also gave rise to a new
idea to treat Parkinson's disease.
Although the mice act very 'hyper',
Caron measured the dopamine contents
in their brains as 'quite low' - about
the same as that in a Parkinson's
patient. In patients with Parkinson's
disease, the idea is to prolong the effect
of what little dopamurc they already
have instead of trying to replenish it.