MID-BRAIN MAY CONTAIN ADDICTION LINK

Addiction to alcohol may be driven in part by a previously unknown brain
signaling pathway discovered by researchers at Oregon Health & Science
University.

Researchers said the system of brain cells and signaling molecules appears
to act separately from the better-known dopamine reward system, which has
been the focus of addiction research for years.

"It seems to be an independent system," said study co-author Andrey
Ryabinin, an assistant professor of behavioral neuroscience at OHSU. The
study was published recently in the Journal of Neuroscience.

The findings point the way to unexplored territory for seeking new
alcoholism treatments using drugs that block or modify the signaling
pathway to reduce addictive cravings.

Ryabinin and colleagues made use of a peculiar family of laboratory mice,
known for a strong lust for alcohol. After allowing the mice a final
drinking binge, the researchers dissected their brains to study how the
pattern of gene expression might differ from other mice -- an inbred strain
with little taste for alcohol.

The experiments led researchers to a cluster of brain cells, called the
Edinger-Westphal nucleus, in the midbrain. The structure exists in human
brains, where its best-known job is the subconscious control of the eyes'
pupil size. But in the drink-loving mice, the cluster of brain cells kicks
into high gear after alcohol consumption.

These brain cells produce a compound called urocortin, originally
discovered in 1995. What it does remains uncertain. Scientists at the Salk
Institute for Biological Studies gained a broad patent on urocortin in
2001, claiming uses in controlling blood pressure, decreasing inflammation,
improving memory and elevating mood.

In the mouse experiments, Ryabinin and collaborators at Indiana University
found that urocortin signaling may be crucial to the animals' alcohol
seeking. Mice that consume large quantities of alcohol have high levels of
urocortin in their brains. Teetotalers have low urocortin levels. The
association held true in other strains of mice, and in the offspring of
imbibers mated to teetotalers.

"That is very compelling evidence, I think, to suggest that this may
actually be a neurochemical pathway involved in alcohol consumption," said
Todd Thiele, an assistant professor of psychology at the University of
North Carolina, who was not involved in the study.

But Thiele said much additional work needs to be done to nail down that
conclusion. He would like to see the findings repeated in other reliable
animal models of addiction, such as rats.