UBC research links addiction and genetics
Scientists engineer mice to resist cocaine’s habit-forming qualities
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 genetics.
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 cocaine.
“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 said.
“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.