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By stimulating one part of the brain with laser
light, researchers at the National Institutes of
Health (NIH) and the Ernest Gallo Clinic and
Research Center at UC San Francisco (UCSF) have
shown that they can wipe away addictive behavior in
rats – or conversely turn non-addicted rats into
compulsive cocaine seekers.
"When we turn on a laser light in the prelimbic
region of the prefrontal cortex, the compulsive
cocaine seeking is gone," said Antonello Bonci, MD,
scientific director of the intramural research
program at the NIH's National Institute of Drug
Abuse (NIDA), where the work was done. Bonci is also
an adjunct professor of neurology at UCSF and an
adjunct professor at Johns Hopkins University.
Described this week in the journal Nature, the new
study demonstrates the central role the prefrontal
cortex plays in compulsive cocaine addiction. It
also suggests a new therapy that could be tested
immediately in humans, Bonci said.
Any new human therapy would not be based on using
lasers, but would most likely rely on
electromagnetic stimulation outside the scalp, in
particular a technique called transcranial magnetic
stimulation (TMS). Clinical trials are now being
designed to test whether this approach works, Bonci
added.
One of the hallmarks of cocaine addiction is
compulsive drug taking – the loss of ability to
refrain from taking the drug even if it's destroying
one's life.
What makes the new work so promising, said Bonci, is
that Billy Chen of NIDA, the lead author of the
study, and his colleagues were working with an
animal model that mimics this sort of compulsive
cocaine addiction. The animals, like human addicts,
are more likely to make bad decisions and take
cocaine even when they are conditioned to expect
self-harm associated with it.
Electrophysiological studies involving these rats
have shown that they have extremely low activity in
the prefrontal cortex – a brain region fundamental
for impulse control, decision making and behavioral
flexibility. Similar studies that imaged the brains
of humans have shown the same pattern of low
activity in this region in people who are
compulsively addicted to cocaine.
To test whether altering the activity in this brain
region could impact addiction, Chen and his
colleagues employed a technique called optogenetics
to shut the activity on and off using a laser.
First they took light-sensitive proteins called
rhodopsins and used genetic engineering to insert
them into neurons in the rat's prefrontal cortex.
Activating this region with a laser tuned to the
rhodopsins turned the nerve cells on and off.
Turning on these cells wiped out the compulsive
behavior, while switching them off turned the
non-addicted ones into addicted, researchers found.
What's exciting, said Bonci, is that there is a way
to induce a similar activation of the prelimbic
cortex in people through a technique called
transcranial magnetic stimulation (TMS), which
applies an external electromagnetic field to the
brain and has been used as a treatment for symptoms
of depression.
Bonci and his colleagues plan to begin clinical
trials at NIH in which they will use this technique
a few sessions a week to stimulate the prefrontal
cortex in people who are addicted to cocaine and see
if they can restore activity to that part of the
brain and help them avoid taking the drug.
For more information
In addition to UCSF, the authors of this study are
affiliated with the National Institute on Drug Abuse,
the Ernest Gallo Clinic and Research Center and the
Solomon H. Snyder Neuroscience Institute, Johns
Hopkins School of Medicine.
This work was funded by the National Institute on
Drug Abuse.
For more information
The article, "Rescuing cocaine-induced prefrontal
cortex hypoactivity prevents compulsive cocaine
seeking" is authored by Billy T. Chen, Hau-Jie Yau,
Christina Hatch, Ikue Kusumoto-Yoshida, Saemi L. Cho,
F. Woodward Hopf and Antonello Bonci. It is
published online by the journal Nature on April 3,
2013. After that date, the article can be accessed.
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12024.html
(MDN)
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