FDA-Approved Drug Might Prevent Relapse In Male
Alcoholics
Source: UCSF press release
Date: November 3, 2011
Mifepristone, a drug approved by the Food and Drug
Administration for terminating early pregnancy, might
prove effective in preventing stress-induced relapse in
recovering male alcoholics, based on findings in rats
reported by researchers at the Ernest Gallo Clinic and
Research Center at the University of California, San
Francisco.
Mifepristone was originally marketed under the name
RU-486. It blocks the activity of progesterone and
cortisol, hormones that, in the brain, are thought to
play a role in promoting alcoholism as well as relapse.
“It’s well-known that stress can lead to relapse
in people who are trying not to drink,” said senior
author Selena E. Bartlett, PhD, director of medications
development at the Gallo Center. “Until now, we have
had very few interventions that showed potential as
possible treatments.”
In an experiment reported online November 2, 2011 in
Neuropsychopharmacology, Bartlett and her research team
trained a group of male rats to drink either an alcohol
solution or a sucrose solution on demand by pressing a
lever. The rats were then conditioned not to press the
lever to seek the reward of a drink – a process
“sort of like rehabilitation in humans,” according
to Bartlett.
After this period of forced abstinence, the rats
were given yohimbine, a compound known to induce stress
and relapse-like behavior in rodents.
“We wanted to see if the stressed rats would press
the lever again, much as a stressed alcoholic in
recovery might reach for a drink,” said Bartlett.
Some of the rats were given injections of
mifepristone before being given yohimbine. Those
animals were significantly less likely to press the
lever for a drink when compared with rats not given
mifepristone.
In order to pinpoint exactly where the mifepristone
was acting in the rats’ brains, Bartlett and her team
repeated the experiment – but this time, before
administering yohimbine, they infused mifepristone
directly into the central nucleus of the amygdala, a
brain structure known to play a role in stress, anxiety
and anxiety disorders. This brain region has been shown
to be a critical area for the control of fear
responses, as well as the center of individual
emotional experience.
The researchers found that the mifepristone
infusions discouraged lever-pressing behavior in the
rats trained to drink alcohol, but not in the rats
trained to drink sucrose solution.
“This was a very unexpected finding, but very
exciting,” said Bartlett. “Identifying the area of
the brain where mifepristone acts to discourage
alcoholic relapse opens up the possibility of creating
new compounds that are even more specific in their
action.”
Currently, Bartlett and her team are working to
determine which hormone mifepristone specifically
blocks in discouraging relapse: cortisol or
progesterone. “We are working to obtain funding to
enable testing of this medication in male
alcoholics,” she said.
Co-authors of the paper are Jeffrey A. Simms, BS, of
the Gallo Center; Carolina L. Haass-Koffler, PharmD, of
the Gallo Center and UCSF; and Jade Bito-Onon, BS, and
Rui Li, BS, of the Gallo Center.
The research was supported by funds from the State
of California through UCSF and the U.S. Department of
Defense.
The UCSF-affiliated Ernest Gallo Clinic and Research
Center is one of the world’s preeminent academic
centers for the study of the biological basis of
alcohol and substance use disorders. Gallo Center
discoveries of potential molecular targets for the
development of therapeutic medications are extended
through preclinical and proof-of-concept clinical
studies.
UCSF is a leading university dedicated to promoting
health worldwide through advanced biomedical research,
graduate-level education in the life sciences and
health professions, and excellence in patient care.
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