UCSF Gallo scientists show that drinking releases
brain endorphins: study offers possible clue to why
alcohol is addicting
Source: UCSF press release
Date: January 11, 2012
Drinking alcohol leads to the release of endorphins
in areas of the brain that produce feelings of pleasure
and reward, according to a study led by researchers at
the Ernest Gallo Clinic and Research Center at the
University of California, San Francisco.
The finding marks the first time that endorphin
release in the nucleus accumbens and orbitofrontal
cortex in response to alcohol consumption has been
directly observed in humans.
Endorphins are small proteins with opiate-like
effects that are produced naturally in the brain.
“This is something that we’ve speculated about
for 30 years, based on animal studies, but haven’t
observed in humans until now,” said lead author
Jennifer Mitchell, PhD, clinical project director at
the Gallo Center and an adjunct assistant professor of
neurology at UCSF. “It provides the first direct
evidence of how alcohol makes people feel good.”
The discovery of the precise locations in the brain
where endorphins are released provides a possible
target for the development of more effective drugs for
the treatment of alcohol abuse, said senior author
Howard L. Fields, MD, PhD, a professor of neurology and
Endowed Chair in Pharmacology of Addiction in Neurology
at UCSF and director of human clinical research at the
Gallo Center.
The study appears on January 11, 2012, in Science
Translational Medicine.
The researchers used positron emission tomography,
or PET imaging, to observe the immediate effects of
alcohol in the brains of 13 heavy drinkers and 12
matched “control” subjects who were not heavy
drinkers.
In all of the subjects, alcohol intake led to a
release of endorphins. And, in all of the subjects, the
more endorphins released in the nucleus accumbens, the
greater the feelings of pleasure reported by each
drinker.
In addition, the more endorphins released in the
orbitofrontal cortex, the greater the feelings of
intoxication in the heavy drinkers, but not in the
control subjects.
“This indicates that the brains of heavy or
problem drinkers are changed in a way that makes them
more likely to find alcohol pleasant, and may be a clue
to how problem drinking develops in the first place,”
said Mitchell. “That greater feeling of reward might
cause them to drink too much.”
Before drinking, the subjects were given injections
of radioactively tagged carfentanil, an opiate-like
drug that selectively binds to sites in the brain
called opioid receptors, where endorphins also bind. As
the radioactive carfentanil was bound and emitted
radiation, the receptor sites “lit up” on PET
imaging, allowing the researchers to map their exact
locations.
The subjects were then each given a drink of
alcohol, followed by a second injection of radioactive
carfentanil, and scanned again with PET imaging. As the
natural endorphins released by drinking were bound to
the opioid receptor sites, they prevented the
carfentanil from being bound. By comparing areas of
radioactivity in the first and second PET images, the
researchers were able to map the exact locations —
areas of lower radioactivity — where endorphins were
released in response to drinking.
The researchers found that endorphins released in
response to drinking bind to a specific type of opioid
receptor, the Mu receptor.
This result suggests a possible approach to
improving the efficacy of treatment for alcohol abuse
through the design of better medications than
naltrexone, said Fields, who collaborated with Mitchell
in the design and analysis of the study.
Fields explained that naltrexone, which prevents
binding at opioid receptor sites, is not widely
accepted as a treatment for alcohol dependence —
“not because it isn’t effective at reducing
drinking, but because some people stop taking it
because they don’t like the way it makes them
feel,” said Fields.
“Naltrexone blocks more than one opioid receptor,
and we need to know which blocking action reduces
drinking and which causes the unwanted side effects,”
he said. “If we better understand how endorphins
control drinking, we will have a better chance of
creating more targeted therapies for substance
addiction. This paper is a significant step in that
direction because it specifically implicates the Mu
opioid receptor in alcohol reward in humans.”
Co-authors of the study are James P. O’Neill and
Mustafa Janabi of Lawrence Berkeley Laboratory and
Shawn M. Marks and William J. Jagust, MD, of LBL and
the University of California, Berkeley.
The study was supported by funds from the Department
of Defense and by State of California Funds for
Research on Drug and Alcohol Abuse.
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.
