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From: NIH news releases and news items [mailto:[log in to unmask]] On Behalf
Of NIH OLIB (NIH/OD)
Sent: Tuesday, March 06, 2007 15:44
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Subject: STUDY ADVANCES EVIDENCE FOR RECEPTOR'S ROLE IN ALCOHOL PLEASURE AND
PROBLEMS
U.S. Department of Health and Human Services NATIONAL INSTITUTES OF HEALTH NIH
News National Institute on Alcohol Abuse and Alcoholism (NIAAA)
<http://www.niaaa.nih.gov/>
FOR IMMEDIATE RELEASE: Tuesday, March 6, 2007
CONTACT: NIAAA Press Office, 301-443-3860, <e-mail: [log in to unmask]>
STUDY ADVANCES EVIDENCE FOR RECEPTOR'S ROLE IN ALCOHOL PLEASURE AND PROBLEMS
A genetic variant of a receptor in the brain's reward circuitry heightens the
stimulating effects of early exposures to alcohol and increases alcohol
consumption, according to a new study by researchers at the National Institute
on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of
Health (NIH). Conducted in rhesus monkeys, the study extends previous research
that suggests an important role for a similar brain receptor variant in the
development of human alcohol use disorders. A report of the findings is
published in the March, 2007 issue of the "Archives of General Psychiatry."
"Although the pathway to alcoholism is influenced by many factors, our findings
affirm that individuals who possess this receptor variant may experience
enhanced pleasurable effects from alcohol that could increase their risk for
developing alcohol abuse and dependence," notes Markus Heilig, M.D., Ph.D.,
NIAAA Clinical Director and the study's senior author.
Molecules known as opioid peptides bind to opioid receptors in the brain to
signal experiences of reward and reinforcement, as well as the euphoria and
other positive subjective effects produced by alcohol. Previous studies have
shown that, among the brain's various subtypes of opioid receptors, the
mu-subtype is most likely responsible for transmitting alcohol's positive
effects.
"We also know that there are several genetic variants of the human mu-opioid
receptor," notes first author Christina Barr, V.M.D., Ph.D., a lead investigator
in NIAAA's Laboratory of Clinical and Translational Studies and Laboratory of
Neurogenetics. "One of these, designated 118G, has a greatly enhanced ability
to bind opioid peptides. People who have this variant of the receptor have
reported increased euphoria following alcohol consumption."
Drs. Barr, Heilig, and their colleagues note that recent studies have linked the
118G mu-opioid receptor with alcohol dependence in humans. In the current
study, the researchers explored the link between genetic variants of mu-opioid
receptors and alcohol-related behaviors in a group of 82 rhesus monkeys.
"A mu-opioid receptor variant that is functionally similar to the human 118G
variant occurs in these animals," explained Dr. Barr. "That is, it also has a
greatly enhanced ability to bind opioid peptides. We hypothesized that monkeys
that had the gene for this receptor variant would experience enhanced alcohol
stimulation and, therefore, consumption.
Groups of monkeys had access to both alcoholic and non-alcoholic solutions for
one hour per day for a period of six weeks. Researchers measured the animals'
alcohol intake and post-intake activity, and determined which monkeys carried
the gene for the mu-opioid receptor similar to the human 118G receptor.
Activity measures are commonly used in animal studies to assess alcohol's
pleasurable effects. As predicted, the researchers found that monkeys with the
variant gene showed increased activity following alcohol consumption. They also
found that male animals with the variant had a clear preference for the alcohol
solution and consumed on average almost twice as much alcohol as other animals.
Males with the variant also became intoxicated on almost 30 percent of testing
days, while other animals did so only on an average of 8 percent of testing
days.
"The male-restricted effect of this gene is interesting, and parallels other
recent evidence that opioid transmission may play a greater role in alcohol
problems among some males than among females," explained Dr. Heilig. This
information also complements recent data suggesting that alcohol-dependent
people with the gene for the 118G receptor have a better therapeutic response to
medications that block opioid receptors. More broadly, the finding underscores
the important role that the pleasurable and stimulating initial effects of
alcohol play in the subsequent development of alcohol problems."
The National Institute on Alcohol Abuse and Alcoholism, part of the National
Institutes of Health, is the primary U.S. agency for conducting and supporting
research on the causes, consequences, prevention, and treatment of alcohol
abuse, alcoholism, and alcohol problems and disseminates research findings to
general, professional, and academic audiences. Additional alcohol research
information and publications are available at <http://www.niaaa.nih.gov>.
The National Institutes of Health (NIH) -- The Nation's Medical Research Agency
-- includes 27 Institutes and Centers and is a component of the U. S. Department
of Health and Human Services. It is the primary federal agency for conducting
and supporting basic, clinical, and translational medical research, and it
investigates the causes, treatments, and cures for both common and rare
diseases. For more information about NIH and its programs, visit
<http://www.nih.gov>.
###
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REFERENCES: Barr CS, Schwandt M, Lindell SG, Chen SA, Goldman D, Suomi SJ,
Higley, JD, Heilig M. Association of a Functional Polymorphism in the ?-Opioid
Receptor Gene With Alcohol Response and Consumption in Male Rhesus Macaques.
"Archives of General Psychiatry". 2007;64:369-376
Ray LA, Hutchison KE. A polymorphism of the mu-opioid receptor gene (OPRM1) and
sensitivity to the effects of alcohol in humans. "Alcohol Clin Exp Res." 2004;
28:1789-1795.
-------------------------------
This NIH News Release is available online at:
<http://www.nih.gov/news/pr/mar2007/niaaa-06.htm>.
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