Pubdate: Tue, 14 Feb 2017
Source: Vancouver Sun (CN BC)
Copyright: 2017 Postmedia Network Inc.
Author: Randy Shore
Page: A1


Scientists engineer mice to resist cocaine's habit-forming

Scientists at the University of B.C. have built a better mouse - one
that is indifferent to cocaine.

Unlike normal mice, the genetically engineered rodents did not show
addictive behaviour even after repeated injections of the narcotic
over days, suggesting habitual drug use in humans may be a matter of

While the finding is unlikely to yield a pill that cures addiction any
time soon, it could lead to a test that identifies who is at greatest
risk of addiction and enable people to act on that knowledge, said
Shernaz Bamji, the lead author of a study published Tuesday by the
journal Nature Neuroscience.

The finding provides a biochemical model for addiction based on
previous work at Johns Hopkins University in Baltimore that found
people with genetic mutations associated with a class of proteins in
the brain called cadherins are more prone to substance abuse.
Cadherins help bind cells together and play a role in which brain
circuits are strengthened during learning - even learning that certain
drugs deliver pleasure.

Although Bamji had theorized higher levels of cadherin would lead to
more addictive behaviour, the opposite turned out to be true.

To better understand its role, the researchers engineered mice to
produce excessive cadherin proteins in their brains.

Bamji and her collaborators injected normal and genetically engineered
mice with cocaine and placed them in a distinctly decorated room
within a multi-room cage. On alternating days, the mice were placed in
the other room and injected with saline, co-author Andrea Globa said.

After six days of alternating treatments, the mice were allowed to
move freely to any of the rooms in the cage.

The normal mice greatly preferred the cocaine-associated room, but the
high-cadherin mice didn't much care for it, suggesting the presence of
extra cadherin had somehow interfered with the learned response to

"Addiction is a form of learning in the reward circuits of the brain,"
Bamji said. "Where you don't get synapse strengthening, you aren't
getting learning and you aren't getting addiction."

However, because many synapses in the brain use the same strategy to
learn, a "magic bullet or pill" for addiction is a long way off, Bamji

"Simply increasing cadherin would likely prevent (addicts) from
learning anything new," Bamji said. "That's not a very good trade-off."

Future research might uncover a protein or enzyme more specific to
addiction that functions only in the brain's reward circuitry, which
could be a target for medication.
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