Gallo Center researchers find potential new drug
target for alcohol addiction
Source: UCSF press release
Date: November 1, 2010
Rapamycin, an FDA-approved drug prescribed to
prevent the rejection of transplanted organs, has been
shown for the first time to decrease excessive alcohol
consumption, binge drinking, and alcohol-seeking
behavior in rodents. The finding is in a study by
researchers at the Ernest Gallo Clinic and Research
Center at the University of California, San
Francisco.
The study, led by Dorit Ron, PhD, a Gallo Center
researcher and a professor of neurology at UCSF,
appears in the online Early Edition section of the
“Proceedings of the National Academy of
Sciences.”
The study demonstrated, also for the first time,
that alcohol consumption in rodents activates a key
signaling pathway in the nucleus accumbens, a brain
region that in both rodents and humans is part of the
reward system that affects craving for alcohol and
other addictive substances.
In the brain, that signaling pathway — a complex
of proteins called the Mammalian Target of Rapamycin
Complex 1, or mTORC1 — plays a significant role in
learning and memory. “This makes sense,” says Ron,
“since addiction is a maladaptive form of learning
and memory.” She says that the mTORC1 pathway has
been well-studied in other areas of the body, such as
the immune system, “but has not been explored that
much in the brain.”
Ron notes that rapamycin specifically diminishes the
rodents’ craving for alcohol. It does not change
their desire to consume sucrose. “This is
significant,” she says, “because current
medications used to treat alcohol abuse interfere with
the brain’s reward system in a larger way, blocking
pleasure in general, which discourages people from
taking those medications.”
The study also showed that rapamycin does not lead
to alteration of the rodents’ general motor
coordination or other taste preferences.
Ron emphasizes that the study was conducted on
rodent models designed to mimic human drinking
behavior, and cautions that rapamycin itself — a
powerful drug with side effects — should not
necessarily be considered for immediate use as a
treatment for alcohol abuse. “The important point is
that we have shown that the mTORC1 pathway is a
potential drug target for alcohol abuse disorders,”
she says. “Our laboratory will continue to actively
pursue this line of research.”
Ron notes that rapamycin is currently being
investigated for potential anti-tumor and other
beneficial properties in animal models, “and a new
generation of rapamycin-like compounds that targets the
mTORC1 pathway is being developed. Some of these
compounds look very promising.”
Co-authors of the study are Jeremie Neasta, PhD, and
Sami Ben Hamida, PhD, of the Gallo Center and UCSF,
Quinn Yowell, BS, of the Gallo Center, and Sebastien
Carcinella, PhD, of the Gallo Center and UCSF at the
time the study was performed.
The research was supported by funds from the
National Institutes of Health and the State of
California.
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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