Alcoholics -- so far at least rats addicted to the bitter drop -- can be
saved from relapse following abstinence from drinking by turning off a
trigger in the brain. Israeli and US researchers were able to identify
and deactivate a brain pathway linked to cravings for alcohol, thus
preventing the rodents from seeking alcohol and drinking it.
researchers -- headed by Dr. Segev Barak of Tel Aviv University’s
School of Psychological Sciences and the Sagol School of Neuroscience,
Profs. Dorit Ron and Patrician Janak of the University of California at
San Francisco, on Sunday night published their findings online in
Nature Neuroscience. The study was conducted in the University of California, San Francisco, in the lab of Professor Dorit Ron.
Although the research was conducted in lab
animals, the authors believe it is quite possible that similar studies
will soon test the same treatment strategy in humans, and that the study
paves the way for treatment of other addictions, including tobacco.
of the main causes of relapse is craving, triggered in the memory by
certain cues -- like going into a bar, or the smell or taste of
alcohol,” said Barak, the lead author. “What we learned is that when
rats were exposed to the smell or taste of alcohol there was a small
window of opportunity to target the area of the brain that
reconsolidates the memory of the craving for alcohol and to weaken or
erase the memory -- and thus the craving.”
In the study,
researchers trained rats to voluntarily access 20 percent alcohol
solution in special chambers by pushing levers, and they drank high
amount of alcohol for three months. They were then put through a 10-day
period of abstinence from alcohol.
Later the animals were
exposed to alcohol either by smell or taste. In the first part of the
experiment, rodents were then killed (under anesthesia) and their brains
scanned to identify the neural pathway that retrieved and
reconsolidated -- the memory of the alcohol. They found activation of a
molecular pathway called the mammalian target of rapamycin complex 1
(or, mTORC1). This activation was specific to a select region of the
amygdala, a structure linked to emotional reactions and withdrawal from
alcohol, and cortical regions involved in memory processing.
the second part. the researchers sought to prevent the reconsolidation
of the memory, thus preventing relapse. They found that when the rats
were presented with just a small drop of alcohol, the smell and taste
activated the mTORC1 pathway. Once mTORC1 was activated, the
alcohol-memory stabilized (reconsolidated) and the rats relapsed on the
following days, meaning in this case, that they pushed the lever to
dispense more alcohol.
However, in rats where the mTORC1 pathway
was deactivated using a drug called rapamycin, administered immediately
after the exposure to the cue (smell, taste), there was no relapse to
alcohol seeking the next day, and drinking remained suppressed for up to
14 days, the end point of the study.
“The smell and taste of
alcohol were such strong cues that we could target the memory
specifically without impacting other memories (like a craving for sugar,
for example),” said Barak, who added that he has been doing brain
studies for many years and has never seen such a robust and specific
activation in the brain.
The study is an “important first step
in the research, but more studies are needed to determine whether
rapamycin -- a drug currently approved as an immunosuppressant for
kidney transplant patients -- would have the same effect in humans. In
future research, Barak plans to investigate in his TAU lab whether the
use of behavioral manipulations, in lieu of pharmaceuticals, could
produce similar results.
“One of the main problems in alcoholism
is relapse, and there are not many treatments. Even with an efficient
treatment, 70% to 80% of the patients will relapse in the first year,”
Barak says. “It’s really thrilling that we were able to completely erase
the memory and prevent relapse in these animals. This could be a
revolution in treatment approaches for addiction, in terms of erasing
unwanted memories and thereby manipulating the brain triggers that are
so problematic for people with addictions” he said.
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