Virginia Commonwealth
University researchers have identified several genetic changes in the brains
of mice caused by ethanol, which may help researchers better understand how and
why people become addicted to alcohol.
In the March issue of the Journal of Neuroscience, researchers reported
significant differences in the gene expression patterns regulated by alcohol in
two mouse strains known as B6 and D2. The two mouse strains differ in a number
of behavioral responses to acute alcohol and in their predisposition to drink
alcohol.
Researchers isolated tissue from three different regions of the brain that
are all known to play a role in responses to alcohol and other drugs of abuse.
Using DNA microarrays, which measure the activity of more than 10,000 genes
simultaneously, together with large databases of other biological information,
researchers were able to identify several genes regulated by alcohol that may
play a role in determining genetic differences in behavioral responses to
alcohol.
“These findings help us to better understand the molecular basis for genetic
differences in behavioral response to alcohol and may eventually lead to new
therapeutic approaches for alcoholism,” said Michael Miles, M.D., Ph.D., a
professor in pharmacology, toxicology and neurology, who also has an appointment
in VCU Life Sciences’ Center for the Study of Biological Complexity.
Gene expression refers to how much a given gene is “turned on,” eventually
leading to more or less protein being produced by that particular gene. Changes
in a gene’s expression are thought to be an important mechanism underlying
long-term memory and learning, including that which occurs with addiction to
alcohol or other drugs, Miles said.
In the study, approximately 400 genes were identified as alcohol regulated in
at least one brain region of either mouse strain. According to Miles, most of
these genes showed regulation in only one or the other strain, or in some cases
exposure to alcohol caused genes to be turned on more in one strain while
decreasing expression of the same gene in the other mouse strain. Such
differences are thought to be related to the mechanisms underlying the different
behaviors that the B6 and D2 mice show with alcohol.