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 that habitual drug use in humans may be a matter of genetics.

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

The finding provides a biochemical model for addiction based onprevious work at Johns Hopkins University in Baltimore, Md., that found people with genetic mutations associated with a class of proteins in the brain called cadherins are more prone to substance abuse.

Cadherin helps bind cells together and play a role inwhich brain circuits are strengthened during learning even learning that certain drugs deliver pleasure.

Although Bamji had theorized that 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 collaboratorsinjected 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, said co-author Andrea Globa.

After six days of alternating treatments, the mice wereallowed 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 didnt much care for it, suggesting that the presence of extra cadherin had somehow interfered with the learned response to cocaine.

Normal mice always gravitate to the chamber where they received the drug, looking for that high, but the mutant mice didnt, said Bamji.

The answer to the mysterious result was found inside the membrane of brain cellsthemselves, where cadherin interfered with the ability of a specialized proteinreceptor to functionat the synapse, the point at which neurons communicatewith each other chemically toform memories.

Unable to strengthen the connection between synapses, the brains learning circuitry couldntretaincocaines pleasurable memory.

Addiction is a form of learning in the reward circuits of the brain, she said. Where you dont get synapse strengthening, you arent getting learning and you arent getting addiction.

However, because many synapsesin the brain use the same strategy to learn, a magic bullet or pill for addiction is a long way off.

Simply increasing cadherin would likely prevent (addicts)from learning anything new, she said. Thats not a very good trade-off.

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

rshore@postmedia.com

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Cocaine addiction a matter of genetics, UBC researchers say - Calgary Herald