The following news release is being issued today by the U.S. Department
of Energy's Brookhaven National Laboratory. An electronic version is
available in our online newsroom at:
http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=05-85
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NEWS RELEASE
Number: 05-85
For release: Wednesday, September 7, 2005
Study Examines Role of Cannabinoid Receptors in Alcohol Abuse
Another brain receptor confirmed to affect alcohol intake; may serve as
treatment target
UPTON, NY -- A new set of experiments in mice confirms that a brain
receptor associated with the reinforcing effects of marijuana also
helps to stimulate the rewarding and pleasurable effects of alcohol.
The research, which was conducted at the U.S. Department of Energy's
Brookhaven National Laboratory and was published online September 2,
2005, by the journal Behavioural Brain Research, confirms a genetic
basis for susceptibility to alcohol abuse and also suggests that drugs
designed to block these receptors could be useful in treatment.
"These findings build on our understanding of how various receptors in
the brain's reward circuits contribute to alcohol abuse, help us
understand the role of genetic susceptibility, and move us farther
along the path toward successful treatments," said Brookhaven's
Panayotis (Peter) Thanos, lead author of this study and many others on
"reward" receptors and drinking (see:
http://www.bnl.gov/bnlweb/pubaf/pr/PR_display.asp?prID=05-49 and ,
http://www.bnl.gov/thanoslab).
Earlier studies in animals and humans have suggested that so-called
cannabinoid receptors known as CB1 - which are directly involved in
triggering the reinforcing properties of marijuana - might also
stimulate reward pathways in response to drinking alcohol. Thanos'
group investigated this association in two experiments.
In the first experiment, they measured alcohol preference and intake in
mice with different levels of CB1 receptors: wild type mice with normal
levels of CB1; heterozygous mice with approximately 50 percent levels;
and so-called knockout (KO) mice that lack the gene for CB1 and
therefore have no CB1 receptors. All mice were given a choice of two
drinking bottles, one with pure water and one with a 10 percent alcohol
solution - approximately equivalent to the alcohol content of wine.
Mice with the normal levels of CB1 receptors had a stronger preference
for alcohol and drank more than the other two groups, with the
CB1-deficient mice showing the lowest alcohol consumption.
After establishing each group's level of drinking, the scientists
treated animals with a drug known to block CB1 receptors (SR141716A)
and tested them again. (These animals were also compared with animals
injected with plain saline to control for the effect of the injection.)
In response to the CB1 receptor-blocking drug, mice with normal and
intermediate levels of receptors drank significantly less alcohol
compared to their pre-treatment levels, while KO mice showed no change
in drinking in response to the treatment.
In the second experiment, the scientists compared the tendency of wild
type and KO mice to seek out an environment in which they had
previously been given alcohol. Known as "conditioned place preference,"
this is an established technique for determining an animal's preference
for a drug.
Animals were first conditioned to "expect" alcohol in a given portion
of a three-chambered cage while being given an injection of saline in
the opposite end, and then monitored for how much time they spent in
the alcohol chamber "seeking" the drug. Wild type animals, with normal
levels of CB1, spent more time in the alcohol-associated chamber than
the saline chamber, showing a decided preference, while KO mice (with
no CB1 receptors) showed no significant preference for one chamber over
the other.
"These results support our belief that the cannabinoid system and CB1
receptors play a critical role in mediating the rewarding and
pleasurable properties of alcohol, contributing to alcohol dependency
and abuse," Thanos said.
In addition, the fact that the mice with intermediate levels of CB1
exhibited alcohol preference and intake midway between those with high
levels of receptors and those with none suggests that the genetic
difference between strains quantitatively influences the preference for
and the amount of alcohol consumed. "These results provide further
evidence for a genetic component to alcohol abuse that includes the CB1
gene - the same gene that is important for the behavioral effects of
marijuana," Thanos said.
While it remains unclear exactly how CB1 triggers the rewarding effects
of alcohol, one possibility is that activation of the CB1 receptor
somehow blocks the brain's normal "stop" signals for the production of
dopamine, another brain chemical known to play a role in addiction.
Without the stop signal, more dopamine is released to produce a
pleasure/reward response.
Since blockade of the CB1 receptor with SR141716A appears to
effectively reduce alcohol intake and preference, this study also
suggests that such CB1 receptor-blocking drugs might play an important
role in the future treatment of alcohol abuse.
This study was funded by the Office of Biological and Environmental
Research within the U.S. Department of Energy's (DOE) Office of
Science; by the National Institute on Drug Abuse and the Intramural
Research Program of the NIH, [National Institute on Alcohol Abuse and
Alcoholism]. The DOE has a long-standing interest in research on
addiction that builds, as this study does, on the knowledge of brain
receptors gained through brain-imaging studies. Brain-imaging
techniques such as MRI and PET are a direct outgrowth of DOE's support
of basic physics research.
Note to local editors: Peter Thanos lives in Coram, New York.
One of ten national laboratories overseen and primarily funded by the
Office of Science of the U.S. Department of Energy (DOE), Brookhaven
National Laboratory conducts research in the physical, biomedical, and
environmental sciences, as well as in energy technologies and national
security. Brookhaven Lab also builds and operates major scientific
facilities available to university, industry and government
researchers. Brookhaven is operated and managed for DOE's Office of
Science by Brookhaven Science Associates, a limited-liability company
founded by Stony Brook University, the largest academic user of
Laboratory facilities, and Battelle, a nonprofit, applied science and
technology organization.
--
Sheldon