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Drinking alcohol shrinks critical brain regions in genetically vulnerable mice

By R&D Editors | February 16, 2012

/sites/rdmag.com/files/legacyimages/RD/News/2012/02/BrainVolume-HRx500.jpg

click to enlarge

The scientists used MRI data mapped onto an existing atlas of the mouse brain to compare the effects of drinking ethanol and water on brain volume overall and region-by-region in mice with and without dopamine D2 receptors. Alcohol-drinking mice that lacked dopamine receptors had lower overall brain volume and reduced volume in the cerebral cortex (blue) and thalamus (purple) compared with D2 receptor-deficient mice drinking water. Alcohol-drinking mice with dopamine receptors did not show these deficits in response to drinking alcohol, suggesting that dopamine receptors may be protective against the brain atrophy associated with chronic drinking. Image: Brookhaven National Laboratory

Brain scans of two strains of mice imbibing significant
quantities of alcohol reveal serious shrinkage in some brain regions—but only
in mice lacking a particular type of receptor for dopamine, the brain’s “reward” chemical. The study, conducted at the U.S. Department of Energy’s
Brookhaven National Laboratory and published in Alcoholism: Clinical and Experimental
Research
, provides new evidence that these dopamine receptors,
known as DRD2, may play a protective role against alcohol-induced brain damage.

“This study clearly demonstrates the interplay of genetic and
environmental factors in determining the damaging effects of alcohol on the
brain, and builds upon our previous findings suggesting a protective role of
dopamine D2 receptors against alcohol’s addictive effects,” said study author
Foteini Delis, a neuroanatomist with the Behavioral Neuropharmacology and
Neuroimaging Lab at Brookhaven, which is funded through the National Institute
on Alcohol Abuse and Alcoholism (NIAAA). Co-author and Brookhaven/NIAA
neuroscientist Peter Thanos stated that, “These studies should help us better
understand the role of genetic variability in alcoholism and alcohol-induced
brain damage in people, and point the way to more effective prevention and
treatment strategies.”

The current study specifically explored how alcohol consumption
affects brain volume—overall and region-by-region—in normal mice and a strain
of mice that lack the gene for dopamine D2 receptors. Half of each group drank
plain water while the other half drank a 20% ethanol solution for six months.
Then scientists performed magnetic resonance imaging (MRI) scans on all the
mice and compared the scans of those drinking alcohol with those from the water
drinkers in each group.

The scans showed that chronic alcohol drinking induced
significant overall brain atrophy and specific shrinkage of the cerebral cortex
and thalamus in the mice that lacked dopamine D2 receptors, but not in mice
with normal receptor levels. Mice in both groups drank the same amount of
alcohol.

“This pattern of brain damage mimics a unique aspect of brain
pathology observed in human alcoholics, so this research extends the validity
of using these mice as a model for studying human alcoholism,” Thanos said.

In humans, these brain regions are critically important for
processing speech, sensory information, and motor signals, and for forming
long-term memories. So this research helps explain why alcohol damage can be so
widespread and detrimental.

“The fact that only mice that lacked dopamine D2 receptors
experienced brain damage in this study suggests that DRD2 may be protective
against brain atrophy from chronic alcohol exposure,” Thanos said. “Conversely,
the findings imply that lower-than-normal levels of DRD2 may make individuals
more vulnerable to the damaging effects of alcohol.”

That would in effect deal people with low DRD2 levels a double
whammy of alcohol vulnerability: Previous studies conducted by Thanos and
collaborators suggest that individuals with low DRD2 levels may be more
susceptible to alcohol’s addictive effects.

“The increased addictive liability and the potentially
devastating increased susceptibility to alcohol toxicity resulting from low
DRD2 levels make it clear that the dopamine system is an important target for
further research in the search for better understanding and treatment of
alcoholism,” Thanos said.

SOURCE

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