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Brain
chemistry ties Anxiety and Alcoholism
Newswise — Doctors may
one day be able to control alcohol addiction
by manipulating the molecular events in the
brain that underlie anxiety associated with
alcohol withdrawal, researchers at the
University of Illinois at Chicago College of
Medicine and the Jesse Brown VA Medical
Center report in the March 5 issue of the
Journal of Neuroscience.
"The association of
anxiety with increased alcohol use is a key
factor in the initiation and maintenance of
alcohol addition," says Dr. Subhash Pandey,
UIC professor of psychiatry and director of
neuroscience alcoholism research, the lead
author of the study.
Previous research has
shown that people with inherently high
levels of anxiety are at an increased risk
of becoming alcoholics. In addition,
withdrawal of alcohol in chronic users is
often accompanied by extreme anxiety.
"Alcoholics may feel a
need to continue to drink alcohol in an
attempt to self-medicate to reduce their
anxiety and other unpleasant withdrawal
symptoms," said Pandey.
Pandey and his
colleagues have discovered the molecular
basis for the link between anxiety and
alcohol addiction, which may help in
identifying new therapeutic strategies for
the treatment of alcohol addiction.
The researchers found
that a protein within neurons in the
amygdala -- the area of the brain associated
with emotion and anxiety -- controls the
development of alcohol withdrawal symptoms
and drinking behaviors in laboratory animals
by changing the shape of the neurons. This
change in shape affects the communication
between neurons, leading to changes in
behavior.
Neurons communicate by
sending signals through branches called
dendritic spines. The researchers found that
short-term alcohol exposure increased the
number of dendritic spines in certain
regions of the amygdala, producing
anti-anxiety effects. Alcohol-dependent
animals eventually developed a tolerance to
the anxiety-lowering effects of alcohol.
The researchers traced
the anti-anxiety effect to the production of
a particular protein, Arc, in response to a
nerve growth factor called BDNF that is
stimulated by alcohol exposure. BDNF is
vital in the functioning and maintenance of
neurons.
When alcohol was
withheld from animals that had been
chronically exposed, they developed high
anxiety. Levels of BDNF and Arc -- and the
number of dendritic spines -- were decreased
in the amygdala. But the researchers were
able to eliminate the anxiety in the
alcohol-dependent animals by restoring BDNF
and Arc to normal levels.
Pandey suggested that
an initial easing of anxiety may encourage
people to begin to use alcohol, while for
chronic users, a lack of alcohol provokes
high anxiety, creating a need to continue
drinking to feel normal.
The researchers blocked
Arc production in normal rats by injecting a
complementary sequence to Arc gene DNA into
the central amygdala.
They found that when
levels of Arc in the central amygdala were
lowered, the spines decreased and anxiety
and alcohol consumption increased.
When levels of Arc were
returned to normal three days
post-injection, anxiety and alcohol
consumption also returned to normal.
In a previous study,
researchers found that lowering BDNF in
amygdala promoted anxiety and alcohol
drinking.
"This is the first
direct evidence of the molecular processes
occurring in the neurons that is responsible
for the co-morbidity of anxiety and
alcoholism, which we believe plays a major
role in the addictive nature of alcohol,"
said Pandey.
"This offers the
possibility of new therapeutic target --
BDNF-Arc signaling and associated dendritic
spines in the amygdala -- or new drug
development."
"These observations by
Dr. Pandey's research group provide an
insight into the link between alcohol and
anxiety and could be used to identify new
targets for developing medications that
alleviate withdrawal-induced anxiety and
potentially modify a motivation for
drinking," said Antonio Noronha, director of
neuroscience and behavior research at the
National Institute on Alcohol Abuse and
Alcoholism.
The work was supported
by grants from the National Institute on
Alcohol Abuse and Alcoholism and the
Department of Veterans Affairs. Huaibo
Zhang, Rajesh Ugale, Anand Prakash, Tiejun
Xu and Kaushik Misra of the UIC College of
Medicine and the Jesse Brown VA Medical
Center also contributed to the study.
For more information
about UIC, visit
http://www.uic.edu.
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